Door latch mechanism for drug delivery device

ABSTRACT

A drug delivery device includes a housing defining a shell and an inner volume, a cassette, a door coupled to the housing, a drive mechanism, and a latching assembly. The cassette is removably disposed within the inner volume and is adapted to contain a drug to be administered to a user. The door at least partially encloses the inner volume of the housing and includes a first end defining a latching portion. The drive mechanism is at least partially disposed within the housing and exerts a force to urge the drug out the cassette. The latching assembly is coupled to the drive mechanism and includes a first end and a second end. Upon actuating the drive mechanism, the drive mechanism causes the latching assembly to engage the latching portion of the door to secure the door to the housing.

CROSS-REFERENCE TO RELATED APPLICATION

The priority benefit of U.S. Provisional Patent Application No.62/587,391, filed Nov. 16, 2017, is claimed, and the entire contentsthereof are expressly incorporated herein by reference.

FIELD OF THE DISCLOSURE

The disclosure relates to injection systems and apparatus. Moreparticularly, the disclosure relates to an autoinjector apparatuscomprising an autoinjector and a cassette useable with the autoinjector,which conceals an injection needle of a drug container before and afteran injection.

BACKGROUND

Drug delivery devices, such as injectors, are used to deliver liquiddrugs to a patient. Upon activation, a drug delivery device will expel adrug stored within an internal reservoir through a needle, cannula, orother delivery member into the patient. Some drug delivery devices, suchas on-body injectors, may be temporarily attached to a patient todeliver a drug via an injection needle or some other means over anextended period of time. The drug delivery device may be adhesivelyattached to the tissue of the patient's abdomen, thigh, arm, or someother portion of the patient's body.

Some devices may have drawbacks. Specifically, users may be frightenedby an exposed injection needle or feel they are inherently incapable ofperforming an injection. Because of aversions to exposed needles, aswell as health and safety issues that may be involved, various types ofinjectors and other devices have been developed for concealing needlesfrom the user and automating the injection task to assist the user inperforming the injection, ensure reliable delivery of the medication andensure patient safety.

Typically, three tasks may be performed when injecting a drug into apatient with a hypodermic syringe: 1) insertion of the needle into thepatient; 2) injection of the drug from the syringe into the patient; and3) withdrawal of the needle after the injection has been completed. Foreach task, the magnitude and direction of forces on the syringe, as wellas the location of their application, may be different from the othertasks. For example, insertion of the needle may require the applicationof a minimal force on the syringe, for a very short period of time. Onthe other hand, injection of the medicament (aka drug) may require theapplication of a much greater force on the plunger of the syringe, andthis force may need to be applied for a relatively longer period oftime. Further, needle withdrawal may require the application of a forcein an opposite direction from needle insertion. These, and other similarconsiderations, may become relevant when the injection process is to beautomated.

In addition to these mechanical considerations, the design of anautoinjector may require user-friendly considerations. In particular, itmay be desirable for the injection needle of the syringe to beoperationally concealed from the view of a user. Preferably, thisconcealment is maintained before, during and after an injectionprocedure. Further, it may be desirable that operation of the syringe belimited to only those times when the syringe is properly positioned foran injection and/or when the appropriate sequence of actions areperformed by the user.

In some cases, a drug delivery device may have a removable door memberthat provides access to the housing to insert a container or cassettecontaining a medicament (aka drug) to be administered. Upon loading thecassette into the housing, the door member must be secured to preventthe cassette from being damaged. Some existing systems are bulky andcostly, and may lead to patient uncertainty as to whether the device isready for administration and/or partial dosing due to the cassette beingimproperly installed or secured in the housing by the patient.

SUMMARY

One aspect of the present disclosure provides a drug delivery devicethat includes a housing defining a shell and an inner volume, acassette, a door coupled to the housing, a drive mechanism, and alatching assembly. The cassette is removably disposed within the innervolume and is adapted to contain a medicament (aka drug) to beadministered to a user. The door at least partially encloses the innervolume of the housing and includes a first end defining a latchingportion. The drive mechanism is at least partially disposed within thehousing and exerts a force to urge the medicament (aka drug) out thecassette. The latching assembly is coupled to the drive mechanism andincludes a first end and a second end. Upon actuating the drivemechanism, the drive mechanism causes the latching assembly to engagethe latching portion of the door to secure the door to the housing.

In some examples, the latching assembly includes a tube cap movablycoupled to the drive mechanism, a slotted latch housing coupled to theshell of the housing, and a latch member slidably coupled to the slottedlatch housing. The tube cap has a first engaging surface and a secondengaging surface. The slotted latch housing has a first end, a secondend, and a slot extending between the first end and the second end. Thelatch member is movable along a length of the slot, and further has afacing surface and a protrusion extending outwardly from the facingsurface to engage the latching portion of the door. The first engagingsurface of the tube cap engages the facing surface of the latch membersuch that movement of the tube cap causes the latch member to move alongthe length of the slot.

In other examples, the latch assembly is movable between at least afirst position whereby the protrusion is disengaged from the latchingportion of the door, a second position whereby the protrusion partiallyengages the latching portion of the door, and a third position wherebythe protrusion fully engages the latching portion of the door torestrict the door from opening. The latching portion of the door mayinclude an angled leading surface to engage the protrusion.

The latch assembly may further include a resilient member to urge thelatch member towards the second end of the slotted latch housing. Insome forms, the drive mechanism further includes a plunger rod. The tubecap may be slidably coupled to the plunger rod. In some approaches, uponremoving the door to insert a cassette into the inner volume of thehousing, the latch assembly moves to the second position prior toclosing the door.

In some examples, the door is coupled to the housing via a hingedconnection. Further, the latching portion of the door may include agroove to restrict movement of the door.

A second aspect of the present disclosure provides a latching assemblyfor a drug delivery device that is actuated by a drive mechanism atleast partially disposed in the drug delivery device. The latchingassembly has a tube cap movably coupled to the drive mechanism, aslotted latch housing adapted to be coupled to the drug delivery device,and a latch member slidably coupled to the slotted latch housing. Thetube cap has a first engaging surface and a second engaging surface. Theslotted latch housing has a first end, a second end, and a slotextending between the first end and the second end. The latch member ismovable along a length of the slot and has a facing surface and aprotrusion extending outwardly from the facing surface to engage alatching portion of a drug delivery device door. The first engagingsurface of the tube cap engages the facing surface of the latch membersuch that movement of the tube cap causes the latch member to move alongthe length of the slot.

A third aspect of the present disclosure provides a method of securing aremovable door to a drug delivery device having a housing defining ashell and an inner volume and a cassette removably disposed within theinner volume of the housing and being adapted to contain a medicament(aka drug) to be administered to a use. A door is coupled to the housingto at least partially enclose the inner volume. The door includes afirst end defining a latching portion. A drive mechanism is at leastpartially disposed in the housing to exert a force to urge themedicament (aka drug) out of the cassette. A latching assembly having afirst end and a second end is coupled to the drive mechanism such thatupon actuating the drive mechanism, the drive mechanism causes thelatching assembly to engage the latching portion of the door to securethe door to the housing.

BRIEF DESCRIPTION OF THE DRAWINGS

The above needs are at least partially met through provision of the doorlatch mechanism for a drug delivery device described in the followingdetailed description, particularly when studied in conjunction with thedrawings, wherein:

The accompanying figures show embodiments according to the disclosureand are exemplary rather than limiting.

FIG. 1 is a side view of an embodiment of an autoinjector apparatuscomprising a cassette and an autoinjector, showing the cassette prior toinstallation in the autoinjector.

FIG. 2A is a front view of the autoinjector apparatus of FIG. 1 showingthe cassette installed in the autoinjector.

FIG. 2B is a side view of a first side of the autoinjector apparatus ofFIG. 1 showing the cassette installed in the autoinjector.

FIG. 2C is a rear view of the autoinjector apparatus of FIG. 1 showingthe cassette installed in the autoinjector.

FIG. 2D is side view of a second side of the autoinjector apparatus ofFIG. 1 showing the cassette installed in the autoinjector.

FIG. 2E is an end view of a first end of the autoinjector of theautoinjector apparatus of FIG. 1.

FIG. 2F is an end view of a second end of the autoinjector of theautoinjector apparatus of FIG. 1.

FIG. 2G is a state diagram showing an embodiment of the decision logicfor controlling a skin sensor of the autoinjector apparatus of FIG. 1.

FIG. 2H is a sectional side view of an embodiment of the autoinjectorapparatus showing the cassette installed in the autoinjector.

FIG. 3 is an exploded perspective view of an embodiment of the cassette.

FIG. 4 is a sectional side view of an embodiment of a drug containerthat can be provided in the cassette.

FIG. 5A is a top down front perspective view of an embodiment of thecassette.

FIG. 5B is a sectional side view of the cassette of FIG. 5A.

FIG. 5C is a sectional side view of the cassette of FIG. 5A afterremoval of a cassette cap of the cassette.

FIG. 5D is a sectional side view of the cassette of FIG. 5C showing aprefilled drug container of the cassette in a needle-injected position.

FIG. 6A is a bottom down front perspective view of an embodiment of thecassette showing an inner sleeve latch mechanism and an inner sleevelocking arrangement.

FIG. 6B is a bottom view of an embodiment of an outer housing of thecassette shown in FIG. 6A showing certain elements of the inner sleevelatch mechanism and the inner sleeve locking arrangement.

FIG. 6C is a bottom up front perspective view of an embodiment of aninner sleeve of the cassette shown in FIG. 3 showing certain elements ofthe inner sleeve latch mechanism and the inner sleeve lockingarrangement.

FIG. 6D is a sectional side view of the cassette of FIG. 6A, showing theoperation of a locking foot of the inner sleeve locking arrangement.

FIGS. 7A-7E are internal side views of the cassette of FIG. 6A showingthe operation of an opening cam of the inner sleeve locking arrangement.

FIGS. 8A and 8B are internal side view of the cassette of FIG. 6Ashowing the operation of an assembly cam of the inner sleeve lockingarrangement.

FIGS. 9A and 9B are top down and bottom down front perspective views,respectively, of an embodiment of the cassette with a cassetteidentification arrangement.

FIG. 10A is a bottom down perspective view of a portion of the cassetteshowing an embodiment of the cassette identification arrangement.

FIG. 10B is a sectional side view of the cassette of FIG. 10A beinginserted into an autoinjector constructed to detect and decipher thecassette identification arrangement embodied in FIG. 10A.

FIG. 11A is a bottom down perspective view of a portion of the cassetteshowing another embodiment of the cassette identification arrangement.

FIG. 11B is a sectional side view of the cassette of FIG. 11A beinginserted into an autoinjector constructed to detect and decipher thecassette identification arrangement embodied in FIG. 11A.

FIG. 12A is a bottom down front perspective view of a portion of thecassette showing another embodiment of the cassette identificationarrangement.

FIG. 12B is a sectional side view of the cassette of FIG. 12A beinginserted into an autoinjector constructed to detect and decipher thecassette identification arrangement embodied in FIG. 12A.

FIG. 13A is a bottom down perspective view of a portion of the cassetteshowing a further embodiment of the cassette identification arrangement.

FIG. 13B is a bottom down perspective view of a portion of the cassetteshowing still another embodiment of the cassette identificationarrangement.

FIG. 13C is a bottom down perspective view of a portion of the cassetteshowing yet another embodiment of the cassette identificationarrangement.

FIG. 13D is a bottom down perspective view of a portion of the cassetteshowing another embodiment of the cassette identification arrangement.

FIG. 14 is a flow chart showing an embodiment of a method for assemblingdifferent product lines on a single manufacturing line using thecassette identification arrangement to control the assembly of prefilleddrug containers (containing a range of different drugs and/or filllevels) and to rout the assembled cassettes to the appropriate packagingstations.

FIG. 15A is a perspective rear view of an embodiment of a cassette capof the cassette.

FIG. 15B is a sectional side view of the proximal end of a cassetteshowing the cassette cap of FIG. 15A coupled to a needle shield of adrug container provided in the cassette.

FIG. 15C is a bottom up front perspective view of a portion of thecassette with the cassette cap removed from the cassette.

FIG. 15D is a sectional side view of the proximal portion of thecassette installed in the autoinjector showing the operation of acantilever lock arm of the cassette cap.

FIG. 16A is a top down front perspective view of a proximal portion ofthe outer housing of the cassette with the cassette cap removed, showingan embodiment of a slot for receiving a key portion of the cassette capembodied in FIG. 15A.

FIG. 16B is a top down front perspective view of the cassette showinghow an anti-rotation structure formed by the slot of the outer housingand the key of the cassette cap prevents the cassette cap from beingrotated or twisted around its longitudinal axis Z when the cassette capis in the cassette (prior to needle shield removal) and thus, preventsrotation of the needle shield.

FIG. 17A is a top down front perspective view of another embodiment ofthe cassette cap having a key portion comprising first and second pairsof tabs.

FIG. 17B is a side view of the cassette cap of FIG. 17A.

FIG. 18A is a top down front perspective view of a proximal portion ofthe outer housing of the cassette with the cassette cap removed, showinganother embodiment of a slot for receiving the tabs of the key portionof the cassette cap embodied in FIG. 17A and ribs disposed in the outerhousing for engaging the tabs provided on the key portion of thecassette cap of FIG. 17A.

FIG. 18B is a top down rear perspective view of a proximal portion ofthe cassette outer housing showing the interior thereof and the ribs.

FIG. 19A is a front perspective view of an interior portion of thecassette with the cassette cap installed, which shows the tabs on oneside of the cassette cap key portion engaged with one of the ribs in thecassette outer housing.

FIG. 19B is a sectional bottom view of a proximal portion of thecassette outer housing with the cassette cap installed, which shows thetabs on the cassette cap key portion engaged with the ribs in thecassette outer housing.

FIG. 20 is a top down front perspective view of the cassette showing howan anti-bending structure formed by the key tabs of the cassette cap andthe ribs of the cassette outer housing prevent flexing or bending of thecassette cap in the vertical axis (X-axis) and horizontal axis(Y-Axis.).

FIG. 21 is a bottom up perspective view of the autoinjector of theautoinjector apparatus or system showing the installation of a cassetteinto the autoinjector.

FIG. 22 is a flow chart showing an embodiment of the decision logic forforcing a user to execute the steps of an injection process in a safeand reliable order.

FIG. 23 is a sectional side view of the drug delivery device showing anextrusion delivery subsystem having a latching mechanism attachedthereto.

FIG. 24 is a sectional side view showing the extrusion deliverysubsystem in an uncoupled configuration with the door.

FIG. 25 is a sectional side view showing engagement between the door anda latching mechanism.

FIG. 26 is a sectional side view showing the extrusion deliverysubsystem in a coupled configuration with the door.

Skilled artisans will appreciate that elements in the figures areillustrated for simplicity and clarity and have not necessarily beendrawn to scale. For example, the dimensions and/or relative positioningof some of the elements in the figures may be exaggerated relative toother elements to help to improve understanding of various embodimentsof the present invention. Also, common but well-understood elements thatare useful or necessary in a commercially feasible embodiment are oftennot depicted in order to facilitate a less obstructed view of thesevarious embodiments. It will further be appreciated that certain actionsand/or steps may be described or depicted in a particular order ofoccurrence while those skilled in the art will understand that suchspecificity with respect to sequence is not actually required. It willalso be understood that the terms and expressions used herein have theordinary technical meaning as is accorded to such terms and expressionsby persons skilled in the technical field as set forth above exceptwhere different specific meanings have otherwise been set forth herein.

DETAILED DESCRIPTION

The present disclosure generally relates to a door latch mechanism for adrug delivery device. Generally, the drug delivery device includes ahousing defining a shell, a cassette having a container, a door coupledto the housing, a drive mechanism, and a latching assembly. The cassettehas a container having an inner volume to contain a medicament (akadrug) to be administered to a user. The drive mechanism is adapted toexert a force on the first end of the container to urge the medicament(aka drug) through the container towards the second end thereof. Thedrive mechanism further is adapted to actuate the latching assembly toselectively couple the door to the housing.

FIG. 1 shows an embodiment of an autoinjector system or apparatus 100that can be used for injecting a dose of pharmaceutical product (drug)into a patient, the injection often being self-administered by thepatient (user). Alternatively, the drug can be administered by ahealth-care provider. As shown, the autoinjection system or apparatus100 may comprise a removable cassette 200 and an autoinjector orinjector 300. Various embodiments of the cassette 200 may be constructedto contain a drug to be injected into the user by the autoinjector 300.In various other embodiments the cassette 200 may be constructed for usein training the user to operate the autoinjector 300 (a trainingcassette). The autoinjector 300 may be constructed to deliver aninjection automatically upon actuation by the user or some other person.Various embodiments of the autoinjector 300 may have a cassette door 308that can be constructed to pivot between and an open position and aclosed position to allow insertion of the cassette 200 into theautoinjector 300. In some embodiments, the cassette door 308 may includea “cassette” icon (not shown) that indicates the insertion entry pointfor the cassette 200. As will be discussed with reference to FIGS.23-26, the autoinjector 300 may include a latching mechanism to securethe door 308 thereto.

Referring collectively to FIGS. 2A-2F, various embodiments of theautoinjector 300 may comprise a shell or casing 302 that defines aninner volume 302 a. The shell 302 has a handle section 304 and acassette receiving section 306 inline with the handle section 304. Toaid patients with manual dexterity issues, the handle section 304 of theautoinjector shell 302 may define an ergonomically shaped handle 305with a soft grip area 305S. The cassette receiving section 306 comprisesthe cassette door 308 (FIGS. 2B and 2D) described earlier. The cassettedoor receives the cassette 200 in an open position (FIG. 1) and alignsthe cassette 200 with insertion and extrusion drives, and otherstructures and components of the autoinjector 300 in a closed position.The cassette door 308 may include a “cassette” icon that indicates theinsertion entry point for the cassette 200. The cassette receivingsection 306 of the shell 302 may comprise windows 310A, 310B on sidesthereof that align with windows of the cassette 200 when the cassettedoor 308 is closed with the cassette 200 correctly installed therein. Inone or more embodiments, the windows 310A, 310B may be double-layered.One or more lights (not shown) may be provided inside the shell 302 toevenly backlight illuminate the cassette windows 212 (FIG. 5A) and thesyringe 260 disposed within the inner sleeve 220 of the cassette 200(FIG. 5B), so that the user can observe the injection cycle through thewindows 310A, 310B of the autoinjector 300, i.e., observe the initialand end positions of the plunger-stopper 264 of the syringe 260 (FIG.5B) during the syringe content (hereinafter “drug”) extrusion process,as well as syringe movements within the cassette 200.

Referring still to FIGS. 2A, 2B, 2D, and 2F, the autoinjector 300 mayfurther comprise a user interface 312 and an audio speaker (not shown).The user interface 312 (best illustrated in FIG. 2A) may be located inthe cassette receiving section 306 of the shell 302, and providesvarious visual indicators. The audio speaker may be disposed inside theshell 302 and provides various audible indicators. The audio speaker mayaudibly communicate with the external environment via a speaker aperture314 formed in the shell 302 in the cassette receiving section 306. Thevisual and audible indicators generated by the user interface 312 andthe audio speaker can tell the user when the autoinjector 300 is readyfor use, the progress of the injection process, injection completion,the occurrence of any errors, and other information. The autoinjector300 may further comprise one or more of a settings/mute switch 315, aspeed selector switch 316, a start button 307, and an eject button 317.The settings/mute switch 315 (FIG. 2B) may be located in the cassettereceiving section 306 of the shell 302. The mute switch 315 may beconstructed allow the user to turn on and off all synthesized sounds,except error sounds, and to respond in real-time so that if the userbegins the injection process and changes the mute switch to off, thesounds are immediately muted. The mute switch 315 may also beconstructed to slide toward a “mute” icon to mute the audio speaker. Alight indicator may be provided to confirm the “mute” state. The speedselector switch 316 (FIGS. 2A and 2B) may be located in the cassettereceiving section 306 of the shell 302. The speed selector switch 316may be constructed to allow the user to select among a plurality ofpreset drug delivery (extrusion) speeds to accommodate personal patientpreference. The speed selector switch 316 may comprise a three switchpositions. Other embodiments of the speed selector switch may comprisetwo switch positions, or 4 or more switch positions. In still otherembodiments, the speed selector switch may be of the infinitely variabletype. In some embodiments, changing the position of the switch 316 priorto injection changes the speed of drug extrusion during injection whilechanging the position of the speed selector switch 316 during injection,does not change the speed of the injection in real time. Theautoinjector 300 may also be provided with one or more demo cassettes toallow the user to experiment with different speeds of drug delivery. Thestart button 307 may be disposed at a free end of the handle 305. Thebutton 307 may include an indentation 3071 (FIG. 2F) for optimizingthumb placement on the button 307. The button 307 may be made of atranslucent material that allows a lighting effect to illuminate thebutton as signals. The eject button 317 (FIG. 2D) may be located in thecassette receiving section 306 of the shell 302. The eject button 317may include an indentation 3171 for optimizing finger placement on thebutton 317. In some embodiments, the eject button 317 may be controlledby the microprocessor 350 (FIG. 2H) of the autoinjector 300, which maybe programmed to eliminate accidental inputs during the injectionprocess.

Referring to FIG. 2E, the cassette receiving section 306 of the shell302 and the cassette door 308 may form a proximal end wall 318 of theautoinjector 300. The proximal end wall 318 may be configured as abroad, flat and stable base for easily positioning the autoinjector 300on a support surface, after removal of the shield remover 240 (FIG. 5A)or when the autoinjector 300 does not contain the cassette 240. Theportion of the proximal end wall 318 formed by the cassette door 308 mayinclude an aperture 308A that is sized and shaped to allow the shieldremover 240 to be removed from the cassette 200 and withdrawn throughthe aperture 308A, when the cassette 200 is installed in theautoinjector 300. The proximal end wall of the autoinjector 300 mayfurther comprise a target light 320. The target light 320 may beconstructed to turn on when the shield remover 240 is removed from thecassette 200 and withdrawn through the aperture 308A, thereby visuallyindicating that the shield remover 240 has been removed. Once turned on,the target light aids the user in visualizing and selecting an injectionsite.

Referring still to FIG. 2E, the autoinjector 300 may further comprise acapacitance-based skin sensor 380 (shown with broken lines) or any othersuitable skin sensor. The skin sensor 380 may coupled to amicroprocessor provided, for example, in the autoinjector 300 in amanner that allows signals or data to be communicated to themicroprocessor, so that the autoinjector 300 can determine when theproximal end wall 318 of the autoinjector 300 touches or contacts skinwithout the need to provide downward pressure on the injection-sitearea. The skin sensor 380 may also be constructed to inform the userthrough audible and visual indicators generated by the speaker and userinterface, when skin contact is detected. In some embodiments, the skinsensor 380 may comprise two pads or electrodes (not shown) locatedadjacent to an inner surface of or embedded in the proximal end wall 318of the autoinjector 300. When the proximal end wall 318 is placed incontact with the skin, the electrode's capacitance signal increases. Ifthe increase is sufficient as determined by the microprocessor, whichmay be programmed with sensor decision logic, that electrode will becomeactivated. To determine whether skin contact has been made, themicroprocessor reads the capacitance of the electrodes. Themicroprocessor then processes the capacitance information from bothelectrodes to determine when the proximal wall 318 makes proper contactwith the skin. In the embodiment where the electrodes are disposed onthe inner surface of the proximal wall 318, the electrodes themselvesnever make contact with skin, only the plastic housing makes contactwith skin, with the electrodes attached to the housing on the inside.Such a design would account for the distance of the electrodes from theskin (spaced by the proximal wall 318) as well as the housing materialresponse in how the calculation determines that the device is in contactwith (or in actuality just very close to) the injection site.

FIG. 2G is a state diagram illustrating the decision logic forcontrolling skin sensor 380 with the microprocessor of the autoinjector300, according to an embodiment of the present disclosure. The processstarts at 400 which represents a reset of the autoinjector. The logicthen flows to state 402 which represents the initialization of the skinsensor after the reset of the autoinjector. Once initialized, the logicflows to state 404 which represents a “no-touch” state where none oronly one of the electrodes of the sensor sense that the proximal endwall 318 touches the skin. If both electrodes sense that the proximalend wall 318 touches skin for less than a certain threshold time period(e.g., one second), the logic flows to state 406 which represents a“touching” state. If one or neither one of the electrodes sense that theproximal end wall 318 touches skin, the logic flows back to state 404.If, however, both electrodes sense that the proximal end wall 318touches skin for a period of time equal to the threshold time period(e.g., one second), the logic flows to state 408 which represents a“touch OK” state. If one electrode or no electrodes sense that theproximal end wall 318 contacts skin, the logic flows to a “releasing”state 409. If both electrodes touch skin, the logic flows back to “touchOK” state 408. If one or no electrodes contact skin for more than thethreshold time period (e.g., more than one second), the logic flows backto “no touch” state 404.

As shown in FIG. 2H, various embodiments of the autoinjector 300 maycomprise a chassis 301 disposed in the shell 302 for supporting amotorized needle insertion drive 330, a motorized drug extrusion drive340, a microprocessor 350, a battery 360 for powering the drives 330,340 and the microprocessor 350, and the skin sensor 380. The shell 302may define an ergonomically shaped handle section 304 and a cassettereceiving section 306. The chassis 301 may include a support surface 301s for supporting one or more cassettes 200 in the autoinjector 300 andaligning the cassette 200 or a selected one of the one or more cassettes200 with motorized needle insertion and drug extrusion drives 330 and340, respectively. A detector 370 may be provided on or in the cassettesupport surface 301 s for sensing the presence of and/or informationabout the cassette 200. The detector 370 may be coupled with themicroprocessor 350 in a manner that allows signals or data to becommunicated to the microprocessor 350. The insertion drive 330 mayinclude an insertion rack 332, an insertion drive motor 331 and aninsertion drive gear train 333 for transmitting rotary motion of theinsertion drive motor 331 to drive the rack 332. The insertion rack mayinclude a tab arrangement including, for example, proximal and distaltabs 332 p and 332 d, respectively, which interface with the cassette200. The extrusion drive 340 may comprise an extrusion drive motor 341,a plunger rod 342, a lead screw 343, and an extrusion drive gear train344. The plunger rod 342 is driven by the extrusion drive motor 341through the lead screw 343 and the extrusion drive gear train 344, andmay interface with a plunger 264 of a drug container 260 containedwithin the cassette 200. The autoinjector 300 can be used for executingmultiple injections.

Referring still to FIG. 2H, the microprocessor 350 of the autoinjector300 may be programmed with instructions that, when executed by themicroprocessor 350, enable it to control and monitor the variousoperations and functions of the autoinjector 300. For example, but notlimitation, the microprocessor 350 may be programmed with instructionsfor controlling the motorized insertion and extrusion drives 330, 340.Such instructions may control and monitor each step of the injectioncycle and process flow, thereby automating needle insertion, drugextrusion, and needle retraction, and controlling the sequence ofactions performed by the user so that the injection process and drugadministration can be made more reliable, accurate, and consistent. Themicroprocessor 350 may also be programmed with instructions forcontrolling the audible and visual feedbacks to the user. An automatedpower-on self-test checks the operation of the autoinjector 300 andremaining battery charge.

In various other embodiments, the autoinjector 300 may include othertypes of needle insertion drives, drug extrusion drives, and means foractivating and sequencing the drives. The insertion and extrusiondrives, in such embodiments may be implemented as separate and distinctmechanisms or combined into a single mechanism. The insertion andextrusion drives of such embodiments may be powered, without limitation,by motors, mechanical mechanisms (e.g., elastic members such assprings), gas pressure mechanisms, gas releasing mechanism, or anycombination thereof. Various transmission mechanisms may be used fortransmitting the power to the cassette, to cause injection of the drug.In addition, the activating and sequencing means may comprise variousmechanical and electromechanical arrangements, which may be combinedwith the microprocessor described earlier or used alone. Theautoinjector in such embodiments may be constructed to be reusable forexecuting multiple injections or be designed for a single, disposableuse.

Referring now to FIG. 3, various embodiments of the cassette 200 maycomprise an outer housing 210, an inner sleeve 220, a drug container 260for containing a drug, a cassette cap 240, a lock cap 230, and a cover250. Such embodiments of the cassette 200 facilitate and enable easyinjection of the drug with the autoinjector and can be constructed for asingle, disposable use. In various embodiments, the lock cap 230 andcover 250 of the cassette 200 may be constructed to resist removal ofthe drug container 260 from the cassette 200, thereby preventing needlesticks before and after use of the cassette 200 and also preventing thedrug container 260 from being taken out of the cassette 200 or replaced.In addition, the lock cap 230 and cover 250 protect the drug container260 during shipment and transportation. The cassette cap 240, in variousembodiments, may be constructed to remove a needle shield 266 coveringan injection needle associated with the drug container 260. In variousother embodiments, the cassette cap 240 may also be constructed toengage the outer housing 210 of the cassette 200, such that the cassettecap 240 cannot be rotated or twisted, thereby preventing the needleshield 266 from damaging the injection needle. Various embodiments ofthe inner sleeve 220 may be constructed to position the drug container260 within the cassette housing 210 in either a needle-concealedposition or a needle injection position during an injection cycle of theautoinjector. In various other embodiments, the outer housing 210 andthe inner sleeve 220 of the cassette 200 may include one or more lockingarrangements that protect the drug container 260 and prevent unintendedneedle exposure or damage. Various other embodiments of the cassette 200may include a cassette identification arrangement that interfaces withthe autoinjector to communicate the installation of the cassette 200within the autoinjector and/or information about the cassette 200.

As shown in FIG. 4, the drug container 260 may comprise a conventionalglass or plastic syringe comprising a barrel 261 that defines a fluidchamber 262. The fluid chamber 262 may be filled for treatment or beprefilled with a predetermined dose of a drug 267. The drug may have aviscosity that depends on the temperature of the product. The syringe260 may further comprise an injection needle 265 removably or fixedlydisposed at a proximal end of the barrel 261, and an outwardly extendingflange 263 disposed at a distal end of the barrel 261. The injectionneedle 265 may communicate with the fluid chamber 262 to allowdispensing of the predetermined dose of the drug 267 expelled from thefluid chamber 262 of the syringe barrel 261. The syringe 260 may furthercomprise a moveable plunger-stopper 264, disposed within the fluidchamber 262 of the barrel 260, for expelling the predetermined dose ofthe drug 267 from the chamber 261 so that it may be dispensed throughthe injection needle 265. A protective needle shield 266 made, forexample, of a non-rigid material, may be provided for covering theinjection needle 265.

In some embodiments, the drug contained in the drug container 260 mayhave a viscosity of about 19 centipoise, at room temperature (20 to 25°C. [68-77° F.]).

In some embodiments, the drug contained in the drug container 260 mayhave a viscosity ranging between about 1 centipoise and about 320centipoise, at room temperature.

In some embodiments, the drug contained in the drug container 260 mayhave a viscosity ranging between about 5 centipoise and about 40centipoise, at room temperature.

In some embodiments, the drug contained in the drug container 260 mayhave a viscosity ranging between about 10 centipoise and about 35centipoise, at room temperature.

In some embodiments, the drug contained in the drug container 260 mayhave a viscosity ranging between about 15 centipoise and about 30centipoise, at room temperature.

In some embodiments, the drug contained in the drug container 260 mayhave a viscosity ranging between about 20 centipoise and about 25centipoise, at room temperature.

In some embodiments, the drug contained in the drug container 260 mayhave a viscosity ranging between about 16 centipoise and about 42centipoise, at room temperature.

In some embodiments, the drug contained in the drug container 260 mayhave a viscosity ranging between about 1 centipoise and about 29centipoise, at room temperature.

Referring collectively to FIGS. 5A-5D, various embodiments of the outerhousing 210 of the cassette 200 may comprise a top wall 210 t, a bottomwall 210 b, side walls 210 s connecting the top and bottom walls 210 tand 210 b, respectively, a front or proximal end wall 210 pe and an openrear or distal end 210 de. The proximal end wall 210 pe of the outerhousing 210 may include an aperture 214 (FIGS. 5C and 5D), which isconstructed to removably receive the cassette cap 240. The outer housing210 may be constructed to retain the inner sleeve 220 therein whileallowing it to be freely moved within the outer housing 210 in aslidable manner after removal of the cassette cap 240 (FIG. 5C). Someembodiments of the outer housing 210 may comprise an elongated openingor window 212 in each side wall 210 s thereof (FIG. 5A). The outerhousing 210 of the cassette 200 may also include a pin 215 (FIG. 5A) orany other suitable mechanical structure that prevents the cassette 200from being inserted into the cassette door in the wrong direction and/ororientation. An “arrow” icon may be provided on the outer housing 210(not shown) to indicate the proper direction and orientation forinserting the cassette into the cassette door.

Referring still to FIGS. 5A-5D, various embodiments of the inner sleeve220 may comprise proximal and distal ends 222 and 224, respectively. Thesleeve 220 may be sized and dimensioned to directly or indirectly holdthe drug container 260 therein in a secure manner. The proximal end 222of the inner sleeve 220 may define an aperture 222 a which isconstructed to allow the injection needle 265 of the drug container 260to extend therethrough (FIG. 5C). The inner sleeve 220 may furthercomprise a drive post 268, which allows it to be driven by the insertiondrive of the autoinjector during the needle insertion cycle of theautoinjector's injection cycle. As can be seen in FIGS. 5C and 5D, theinner sleeve 220 can be driven through the outer housing 210 of thecassette 200 by the insertion drive of the autoinjector, during whichthe drug container 260 moves from a distal position in the outer housing210 (FIG. 5C) to a proximal position in the outer housing 210 (FIG. 5D)and then back to the distal position. When the inner sleeve 220 is inthe distal position (needle-concealed position), as shown in FIG. 5C,the injection needle of the drug container 260 is contained within theouter housing 210 of the cassette 200 and concealed from view by theuser. When the inner sleeve 220 is in the proximal position(needle-injection position), as shown in FIG. 5D, the injection needleof the drug container 260 extends out through the aperture 214 in theproximal end wall 210 pe the outer housing 210 of the cassette 200 andthe autoinjector (not shown). The lock cap 230 closes the open distalend 224 of the inner sleeve 220 thereby locking the drug container 260within the inner sleeve 220, so that the drug container 260 moves withthe inner sleeve 220 as it is driven forward or backward through theouter housing 210 by the insertion drive of the autoinjector, during theinsertion cycle of the autoinjector 300. The cover 250 closes the opendistal end 210 de of the outer housing 210 and prevents tampering withthe drug container 260 by encasing the inner sleeve 220 and the drugcontainer 260 within the outer housing 210 of the cassette 200, and alsocompletes the cosmetic appearance of the cassette 200. The inner sleeve220 may be made from a transparent, rigid material, such as a clearpolycarbonate, to allow viewing of the drug container 260 through thewindows 212 in the side walls 210 s of the outer housing 210.

Referring collectively to FIGS. 6A and 6B, various embodiments of theouter housing 210 of the cassette 200 may comprise a latch mechanism 280that latches the drive post 268 of the inner sleeve 220 to retain thesleeve 220 and, therefore, the injection needle of the drug container,in a needle-concealed position to protect the drug container and preventunintentional needle exposure to the user. As best shown in FIG. 6B, thelatch mechanism 280 may include a pair of resilient, opposing latch arms280 a formed in a bottom wall 210 b of the outer housing 210, or anyother wall of the housing 210 that allows the insertion drive to engagethe drive post 268 of the inner sleeve 220. The latch arms 280 a maydefine locking detent slots 280 b (FIG. 6B) through which the drive post268 of the inner sleeve 220 extends.

During assembly of the cassette 200, the inner sleeve 220 containing thedrug container, may be inserted into the outer housing 210 so that thedrive post 268 of the inner sleeve 220 spreads apart and slides betweenthe latch arms 280 a of the outer housing 210 and then enters thedetents slots 280 b of the latch arms 280 a, where it is latched, asshown in FIG. 6A. During the needle-insertion cycle of the autoinjector,the insertion drive moves the distal tab 332 d in the proximal directionthereby forcing the latch arms 280 a to spread apart and unlatch thedrive post 268 of the inner sleeve 220, thereby allowing proximal anddistal movement of the unlatched inner sleeve 220 through the cassetteouter housing 210, via the drive post 268.

Once unlatched, the insertion drive can move the inner sleeve 220 and,therefore, the drug container disposed therein from the needle-concealedposition to the needle injection position. At the completion of theautoinjector's drug-extrusion cycle, the insertion drive moves the drivepost 268 and, therefore, the inner sleeve 220 containing the spent drugcontainer back to the needle-concealed position where the drive post 268is again latched between the latch arms 280 a of the latch mechanism280.

Referring now to FIGS. 6A-6D, various other embodiments of the cassettemay further comprise an inner sleeve locking arrangement 290, whichprevents the inner sleeve 220 from being unintentionally moved withinthe outer housing 210 from the needle-concealed position. The innersleeve locking arrangement 290 may replace the latch mechanism 280 orprovide redundancy as in the embodiment shown in FIGS. 6A-6B.

The addition of the inner sleeve locking arrangement 290 providesredundancy and increases reliability of the latch mechanism 280, forexample, to protect a user from harm, protect the cassette contents, orprevent misuse. The inner sleeve locking arrangement 290 providesimproved resistance to motion or locking of the inner sleeve 220 duringan impact caused, for example, by a free fall, transportation, and/orhandling. Further, the inner sleeve locking arrangement 290 improvesimpact energy absorption to prevent damage to cassette components. Stillfurther, the inner sleeve locking arrangement 290 provides improvedretention of the inner sleeve 220 in the needle-concealed positionduring removal of the needle shield to prevent exposure of the injectionneedle to the environment outside the outer housing of the cassette 200.In addition, the inner sleeve locking arrangement 290 more accuratelyand repeatedly places the inner sleeve 220 in a position for interfacingwith the autoinjector.

As shown in FIG. 6C, various embodiments of the inner sleeve lockingarrangement may comprise a cantilever lock arm 292, which is constructedto be unlocked by the insertion drive of the autoinjector. Thecantilever lock arm 292 may comprise a hand member 292 h and twoflexible arm members 292 a connecting the hand member 292 h to a portionof the inner sleeve 220. The hand member 292 h may include one or morelocking feet, one or more opening cams, and one or more assembly cams.In the shown embodiment, the hand member 292 h includes two locking feet292 f, one opening cam 292 oc, and one assembly cam 292 ac. The twolocking feet 292 may be spaced apart from one another and disposed at ormarginally adjacent to the leading or proximal edge 292 pe of the handmember 292 h. The opening cam 292 oc may be disposed distal to thelocking feet 292 f and the assembly cam 292 ac may extend proximallyfrom the proximal edge 292 pe of the hand member 292 h. In the shownembodiment, the cantilever lock arm 292 extends from a marginallydistal, bottom portion 220 b of the inner sleeve, or any other portionof the sleeve which is capable of interfacing with the autoinjector'sinsertion drive.

As shown in FIG. 6B, various embodiments of the inner sleeve lockingarrangement 290 may further comprise one or more locking feet receivingslots 294 provided in the bottom wall 210 b of the cassette outerhousing 210, or any other wall of the housing that interfaces with thecantilever lock arm 292 of the inner sleeve 220. Each of the one or morelocking feet receiving slots 294 may be provided at the ends of a pairof elongated slots 282, which define the latch arms 280 a of the latchmechanism 280. Each of the locking feet receiving slots 294 is operativefor receiving a corresponding one of the locking feet 292 f of thecantilever locking arm 292 to effect locking of the inner sleeve lockingarrangement 290.

As shown in FIG. 6D, various embodiments of the locking foot/feet 292 fmay comprise proximal and/or distal faces 292 fp and 292 fd,respectively. The proximal and/or distal faces 292 fp, 292 fd can bedisposed at an angle, which is generally 90 degrees, less than 90degrees (angled forward), or greater than 90 degrees (angled back),relative to the wall of the cassette outer housing 210 defining thelocking feet receiving slots 294, to facilitate locking of the innersleeve locking arrangement. The corresponding surfaces of the lockingfeet receiving slot 294, which engage the proximal and distal faces 292fp, 292 fd of the locking feet 292 f, may be constructed with anglesthat are complimentary to the angles of the proximal and distal faces292 fp, 292 fd of the locking feet 292 f. When the proximal face 292 fpof the locking foot 292 f is angled back as shown in FIG. 6D, and theinner sleeve 220 is forced proximally against the cantilever lock arm292, the locking foot 292 may be drawn deeper into receiving slot 292 ofthe outer cassette housing wall resulting in a bias toward self-locking.Accordingly, the cantilever lock arm 292 can provide a locking forcethat is high relative to the force required to unlock it. In variousother embodiments, the proximal and/or distal faces 292 fp, 292 fd ofthe locking feet 292 f can be angled forward, which may aid in theassembly of the inner sleeve 220 to the outer housing 210. The flexiblearm member(s) 292 a of the cantilever lock arm 292 may apply a biasingforce, which hold each locking foot 292 f in their correspondingreceiving slot 294 in the cassette outer housing wall 210 b. In otherembodiments, the flexible arm member(s) 292 a of the cantilever lock arm292 may not apply a biasing force to hold each locking foot 292 f intheir corresponding receiving slot 294 in the cassette outer housingwall 210 b. The flexible arm members 292 a can bend to disengage thelocking feet 292 f from their receiving slots 294.

Referring to FIG. 6C, in various embodiments, the opening cam 292 oc maybe disposed distal to the locking feet 292 f so that it bends thecantilever lock arm 292 away from the cassette outer housing during theinsertion cycle of the autoinjector. The bending of the cantilever lockarm 292 disengages the locking foot/feet 292 f from the receivingslot(s) 294 in the outer housing and prevents them from contacting andsliding on the outer housing, thereby allowing the inner sleeve 220 tomove freely without interference from the cantilever lock arm 292 duringthe insertion cycle. Various embodiments of the opening cam 292 oc maycomprise a male-shape member having a distal ramp face 296 r that mergeswith a nose face 296 n. The distal ramp face 296 r may be angled back(e.g. where the angle of the distal ramp face 296 r may be less than 270degrees and greater than 180 degrees relative to the nose face 296 n)where it is engaged by the autoinjector's insertion drive, as will beexplained further on. In other embodiments, the opening cam 292 oc maybe configured as a female member.

Referring still to FIG. 6C, various embodiments of the assembly cam 292ac may extend proximally from the proximal edge 292 pe of the handmember 292 h so that it can bend the cantilever lock arm 292 away fromthe cassette outer housing wall 210 b as the inner sleeve 220 isinserted into the outer housing 210 during cassette assembly. Variousembodiments of the assembly cam 292 ac may comprise a male-shape memberhaving a proximal ramp face 298 r that merges with a nose face 298 n.The proximal ramp face 298 r may be angled back (e.g. where the angle ofthe proximal ramp face 298 r may be less than 270 degrees and greaterthan 180 degrees relative to the nose face 298 n) where it contacts thedistal edge of the outer housing bottom wall 210 b when the inner sleeve220 is inserted therein during assembly of the cassette 200. In otherembodiments, the assembly cam 292 ac may be configured as a femalemember.

It should be understood that in various other embodiments, thecomponents of the inner sleeve locking arrangement shown as part of theouter housing in FIG. 6B can be provided on the inner sleeve, and thecomponents of the inner sleeve locking arrangement shown as part of theinner sleeve in FIG. 6C, can be provided on the outer housing. Invarious other embodiments, the number of locking feet, slots, armmembers, and/or cams can be more or less than described above. In stillvarious other embodiments, the cantilever lock arm opening cam can beprovided on the insertion rack of the autoinjector's insertion drive.

Referring to FIGS. 7A-7E, various embodiments of the inner sleevelocking arrangement may operate in the following manner during theinsertion cycle of the autoinjector. FIG. 7A shows the cantilever lockarm 292 after the autoinjector door containing the cassette has justclosed. As shown, the opening cam 292 oc of the lock arm 292 may beproximally spaced from a proximal tab 332 p of the autoinjectorinsertion rack 332, such that the inner sleeve locking arrangement is inthe locked position (i.e., the locking foot/feet of the cantilever armare engaged with their corresponding receiving slot(s) in the cassetteouter housing wall as shown in FIG. 6D). In addition, when the cassetteis loaded and the door is closed, the autoinjector will move the rack332 so that the drive post 268 of the inner sleeve 220 is placed betweenproximal tab 332 p and distal tab 332 d.

FIG. 7B shows the operation of the opening cam 292 oc of the cantileverlock arm 292 after the insertion cycle of the autoinjector has justcommenced. As shown, the proximal tab 332 p of the insertion rack 332has moved proximally to engage the distal ramp face 296 r of the openingcam 292 oc, which bends the arms 292 a of cantilever lock arm 292 andlifts the lock arm 292 toward the inner sleeve 220, thereby disengagingthe locking foot/feet 292 f from the receiving slot(s) (not visible) inthe outer housing bottom wall 210 b. As also shown, the distal tab 332 dof the insertion rack 332 has not engaged the drive post 268 of theinner sleeve 220, however, the resilient arms 280 a of the latchmechanism 280 are about to be unlatched by distal tab 332 d of theinsertion rack 332.

FIG. 7C shows the operation of the opening cam 292 oc of the cantileverlock arm 292 after the proximal tab 332 p of the insertion rack 332 hasmoved further proximally. As shown, the proximal tab 332 p of theinsertion rack 332 has slid under the operating cam 292 oc and isengaged with its nose face 296 n, which fully lifts the cantilever lockarm 292 toward the inner sleeve 220 and, therefore, the lockingfoot/feet 292 f, so they disengage from the receiving slots (notvisible) in the outer housing bottom wall 210 b. Further, the distal tab332 d of the insertion rack 332 has moved proximally and has opened thearms 280 a of the latch mechanism 280, thereby unlatching the drive post268 of the inner sleeve 220 from the latch mechanism 280. The distal tab332 d then engages the drive post 268.

FIG. 7D shows the cantilever arm 292 after needle insertion has beencompleted and the needle retraction has begun. As shown, the proximaltab 332 p of the insertion rack 332 has moved distally, thereby slidingoff the opening cam 292 oc of the lock arm 292 and has engaged the drivepost 268 of the inner sleeve 220. Because the proximal tab 332 p of theinsertion rack no longer engages the opening cam 292 oc, and is movingthe drive post 268 distally, the arms 292 a of the cantilever arm 292bias it down toward the cassette outer housing wall 210 b, therebyallowing the locking foot/feet 292 f of the lock arm 292 to slideagainst the interior surface 210 is of cassette outer housing bottomwall 210 b while holding the assembly cam 292 ac off the interiorsurface of the cassette outer housing wall 210 b, as the inner sleeve220 is driven back to the distal, needle-concealed position in thehousing 210.

FIG. 7E shows the cantilever lock arm 292 after the locking foot/feethave lockingly engaged their corresponding receiving slots 294 (notvisible), thereby placing the inner sleeve locking arrangement back inthe locked position and re-latching the drive post 268 of the innersleeve 220 in the latch mechanism (not visible).

Various embodiments of the inner sleeve locking arrangement may operateto facilitate the assembly of the cassette 200, as will now be describedwith reference to FIGS. 8A and 8B. FIG. 8A shows the cantilever lock arm292 as the inner sleeve 220 is first being inserted into the distal openend 210 de of the outer cassette housing 210 during assembly of thecassette 200. As shown, the cantilever lock arm 292 is in a fully downposition with the arms 292 a relaxed in neutral, unbiased position, andthe angled back proximal ramp surface 298 p of the assembly cam 292 acis contacting a lift ramp 210 r just inside the distal open end 210 deof the cassette outer housing 210.

FIG. 8B shows the cantilever lock arm 292 after the inner sleeve 220 hasbeen inserted further into the cassette outer housing 210. As shown, theassembly cam 292 ac has slid up onto the lift ramp 210 r of the cassetteouter housing 210 facilitated by the angled back proximal ramp face 298r, thereby bending the arms (not visible) of the lock arm 292 andlifting it toward the inner sleeve 220. The lifting of the cantileverlock arm 292 prevents the locking foot/feet 292 f from contacting andthus, interfering with the cassette outer housing 210 as the innersleeve 220 is fully inserted into cassette outer housing 210.

In the above-described embodiments, the inner sleeve locking arrangementprovides inner sleeve locking when the cantilever lock arm is in anunbiased state. In various other embodiments, the cantilever lock arm ofthe inner sleeve locking arrangement can be constructed to provide innersleeve locking in a biased, actuated position. Such embodiments may bedesirable, for example, to hold the inner sleeve and thus, the drugcontainer, in a fixed position at a desired time. In addition, becausethe motor of the insertion drives the sleeve containing the drugcontainer, the depth of the injection needle can be controlled. Thisfeature can be used in conjunction with the locking feet receiving slotsand/or with cassette identification arrangement described further on.

Referring collectively now to FIGS. 9A and 9B, various embodiments ofthe cassette 200 may further comprise a cassette identificationarrangement 410, which may be constructed to communicate informationabout the cassette 200 to the autoinjector. The cassette identificationarrangement 410 may be provided on an exterior surface of the bottomwall 210 bs of the cassette outer housing 210 or any other portion ofthe cassette 200 that is capable of being detected and interpreted bythe autoinjector. In some embodiments the information communicated bythe cassette identification arrangement 410 may be in the form of acode. Specifically, the cassette identification arrangement 410 may beconstructed to generate one of a plurality of different codes, each ofwhich corresponds to certain characteristics of a particular cassette200. The code allows a suitably adapted autoinjector to determine thetype of cassette 200 inserted into the autoinjector, i.e, whether thecassette is a training cassette (i.e., contains no drug receptacle orcontains an empty drug receptacle) or a drug cassette containing thedrug container prefilled with a drug. Further, the code communicated bythe cassette identification arrangement 410 can tell the autoinjectorwhat the drug contained in the drug receptacle is and/or othercassette/drug container characteristics. Still further, the code mayprovide information that allows the autoinjector to determine, whetherthe cassette 200 has been inserted into the autoinjector in the properorientation. The autoinjector can be constructed to automatically selectan appropriate operating program and/or adjust its various operationalparameters based on the information communicated by the cassetteidentification arrangement 410 (e.g., with a microprocessor as describedearlier). For example, if the autoinjector detects the insertion of atraining cassette, the autoinjector can automatically select a trainingprogram to train the user on the use of the autoinjector. In anotherexample, if the autoinjector detects the insertion of a drug cassettethat contains a drug container prefilled with a certain drug, theautoinjector can automatically select appropriate operating parametersfor injecting that drug, such as injection speed, needle insertionspeed, pre and post-injection wait time, needle insertion depth,temperature limits, etc. Available speed ranges may be dependent uponthe drug container fill volume and drug characteristics, such asviscosity. Automatic selection by the autoinjector of its operatingparameters eliminates the need for the user to have to determine theappropriate operating parameters for a given drug and then manuallyinput them into the autoinjector.

As shown in FIG. 10A, various embodiments of the cassette identificationarrangement 410 may comprise one or more projections or tabs 410 tprovided on or in the bottom wall 210 b of the cassette outer housing210. The number and location of the tabs 410 t may define the code or atleast a portion of the code, which represents information about thecassette 200. As shown in FIG. 8B, the cassette identificationarrangement 410 may further comprise a detector 370 that may be providedon or in the cassette support surface 301 s of the autoinjector 300 tosense the number and location of the tabs 410 t when the cassette 200engages the cassette support surface 301 s as the autoinjector door 308is closed. The detector 370 may be communicatively coupled to amicroprocessor 350 contained within the autoinjector 300, therebyenabling the autoinjector 300 to detect the tabs 410 t and obtain thecode representing the information about the cassette 200. In variousembodiments, the detector 370 may comprise a plurality of conventional,flat-flush mounted, momentary, push-button switches 372. The switches372 may be arranged to engage corresponding ones of the tabs 410 t.None, some, or all of the switches 372 may be actuated by the tabs 410 tof the cassette 200, depending upon the arrangement of tabs 410 t andthe code they represent, when the cassette 200 is supported on thecassette support surface 301 s of the autoinjector 300. Therefore, thecode defined by the tabs 410 t and the information that the coderepresents about the cassette 200 can be communicated to themicroprocessor 350 of the autoinjector 300 for deciphering.

The tabs 410 t can be differentiated from each other by their individuallocation on or in the cassette housing 210. By utilizing the presence orabsence of tabs 410 t, multiple combination codes can be created suchthat each code identifies a particular cassette 200 or characteristicsof the cassette. Although the cassette identification arrangement 410shown in the embodiment of FIG. 8A comprises three tabs 410 t, variousother embodiments of the cassette identification arrangement 410 maycomprise more or less than three tabs in order to increase or decreasethe number of programming codes available. In the embodiment shown inFIG. 8A, the presence and/or absence of one or more of the three tabs410 t provides up to eight (8) different possible cassetteidentification codes, which can be detected and deciphered by theautoinjector 300. As mentioned earlier, the information represented byeach code can be used to define one of a plurality of programminginstructions for the autoinjector 300 and/or to communicate secondaryinformation to the autoinjector 300, such as, but not limited to,verifying that the cassette 200 is an authorized OEM device, and/orverifying the proper insertion of the cassette 200 into the autoinjector300.

Various other embodiments of the tabs 410 t of the cassetteidentification arrangement 410 may have different heights. In suchembodiments, the autoinjector's push-button switches 372 andmicroprocessor 350 can be constructed to allow them to differentiatebetween tabs 410 t of the different heights, for example, but notlimitation, by how far in a button (not shown) of the push-button switch372 is depressed into the switch 370 by the tab 410 t. Embodimentscomprising both short and tall tabs 410 t can provide each possible tablocation on the cassette outer housing 210 with one of three possiblestates, e.g.:

State 1: no tab present

State 2: short tab present

State 3: tall tab present

If the cassette identification arrangement 410 comprises, for example,up to three tabs 410 t where each such tab 410 t is short or tall, theautoinjector could detect up to twenty-seven (27) different tab statesto increase the number of possible codes.

As shown in FIG. 11A various other embodiments of the cassetteidentification arrangement 410 may comprise one or more indentations 410i provided in the bottom wall 210 b of the outer housing 210 of thecassette 200. As shown in FIG. 11B, in such embodiments of the cassetteidentification arrangement 410, the detector 370 of the autoinjector 300may comprise a plurality of conventional pogo-pin switches 374 n todetect the presence or absence of the indentations 410 i. The coding,detection, deciphering, and parameter control functions are generallythe same as described above with respect to the tabs 410 t.

Various other embodiments of the indentations 410 i of the cassetteidentification arrangement 410 can have different depths. In suchembodiments, the autoinjector's pogo-pin switches 374 and microprocessor350 can be constructed to allow them to differentiate betweenindentations of the different depths by how far in a pin 374 p of thepogo-pin switch 374 is depressed into the switch by the indentation, toincrease the number of possible different codes.

In various further embodiments, the cassette identification arrangement410 of the cassette may comprise a combination of the above-describedtabs 410 t and indentations 410 i. The autoinjector, in such embodimentsmay then be constructed to include corresponding push-button andpogo-pin switches 372, 374.

The codes defined by the tabs 410 t and/or indentations 410 t of thecassette identification arrangement 410 communicate information aboutthe cassette 200 to the autoinjector 300, which can then use thisinformation to automatically adjust its programming, etc. For example,but not limitation, one tab 410 t or indentation 410 i may define a codethat indicates that the cassette 200 contains a drug container filledwith 1 mL of a drug and two tabs 410 t or indentations 410 i may definea code that indicates that the cassette 200 contains a drug containerfilled with 0.5 mL of a drug. An additional tab 410 t or indentation 410i in the same cassette identification arrangement may provide a codethat identifies the drug and/or characteristics of the drug. In anotherexample, the code for a training cassette may comprise the presence ofall the possible tabs 410 t and/or indentations 410 i. In a furtherexample, the absence of one of the tabs 4105 t and/or indentations 410 imay define a code for a certain drug. Different combinations of tabs 410t and/or indentations 410 i can be used to differentiate betweendifferent drugs or to indicate the absence of the drug container, forthe purpose of controlling the autoinjector parameters.

As shown in FIG. 12A, various other embodiments of the cassetteidentification arrangement 410 may comprise one or more flat,electrically conductive traces or strips 410 s provided on the outersurface of the bottom wall 210 b of the outer housing 210. In suchembodiments of the cassette identification arrangement 410, as shown inFIG. 12B, the detector 370 of the autoinjector 300 can be constructedwith pogo-pin connectors 376 that contact the conductive strips 410 swhen the cassette 200 is inserted into the autoinjector 300. Theconductive strips 410 s can be molded into the exterior surface of thecassette's bottom wall 210 b, screen-printed onto that surface, orcomprise a separate component, such as a flex-cable material, affixed tothat surface with pressure sensitive adhesive or any other suitablemeans.

In various embodiments, the one or more conductive strips 410 s can beoperative as a cassette presence sensor, where each of the conductivestrip 410 s may operate to close an electrical circuit of the detector370 between two pogo-pin connectors 376 when the cassette 200 is mountedon the support surface 301 s of the autoinjector 300. In someembodiments, the conductive strips 410 s can be constructed to form astraight path (e.g., as show in FIG. 12A) to connect inline arrangedpogo-pin connectors, or constructed to form a tortuous path to connectpogo-pin connectors that require jagged or tortuous path to connect. Inother embodiments, the conductive strips 410 s can be constructed tohave a specific electrical resistance, capacitance, inductance, etc,which would define a code capable of detection via the electricalcircuit of the detector 370, which in turn would communicate the codeand, therefore, the associated cassette information to themicroprocessor 350 of autoinjector 300, such as drug, fill volume,injection speed, etc.

As further shown in FIGS. 12A and 12B, various embodiments of thecassette identification arrangement 410 may combine the one or moreconductive strips 410 s with the one or more tabs 410 t (and/orindentions 410 i) described earlier. In such embodiments of the cassetteidentification arrangement 410, the detector 370 and microprocessor 350of the autoinjector 300 can be constructed to have the appropriatepush-button switches 372 and pogo-pin switches 374 (and/or pogo-pinconnectors 376). It should be understood, however, that the cassetteidentification arrangement 410 may only comprise the one or moreconductive strips 410 s.

As shown in FIG. 13A, various other embodiments of the cassetteidentification arrangement 410 may comprise one or more magnets 410 membedded in the bottom wall 210 b of the cassette outer housing 210 orprovided on the exterior or interior surface of the bottom wall 210 b ofthe cassette outer housing 210. In such embodiments of the cassetteidentification arrangement 410, the detector 370 of the autoinjector 300(e.g., FIGS. 10B-12B) can be constructed as a Magnetic Resonance (MR)sensor or other magnetic-sensing sensor that is activated by the one ormore magnets when the cassette 200 is inserted into the autoinjector300. The one or more magnets 410 m should be of sufficient strength toactivate the MR sensor. The magnet and MR sensor arrangement can be usedalone or combined with any of the other previously described cassetteidentification arrangements 410.

As shown in FIG. 13B, various further embodiments of the cassetteidentification arrangement 410 may comprise a radio-frequency (RF)electromagnetic field (EMF) emitting device 410 rf, such as RFidentification (RFID) chip. The detector 370 of the autoinjector 300(e.g., FIGS. 10B-12B) can be constructed as an EMF receiving device,such as an RFID chip reader, that is activated by the RF EMF device 410rf when the cassette 200 is inserted into the autoinjector 300. The RFEMF device 410 rf can be molded into or attached to the bottom wall 210b of cassette outer housing 210 or any other suitable portion of thecassette 200 that allows the RF EMF device 410 rf to communicate withthe detector 370 of the autoinjector 300. In some examples (not shown),the RFID chip may be disposed on or inside of the cassette 200. Forexample, the RFID chip may be disposed on the syringe disposed inside ofthe cassette 200.

As shown in FIG. 13C, various other embodiments of the cassetteidentification arrangement 410 may comprise one or more opticalmachine-readable (OMR) identifiers 4100. The one or more OMR identifiers410 o may comprise, without limitation, one or more bar-code labels, oneor more color-coded labels, one or more other suitable OMR identifiers,or any combination thereof. OMR identifiers 410 o embodied as bar-codelabels may comprise, but are not limited to, 1-dimensional and2-dimensional matrix codes. The detector 370 of the autoinjector 300(e.g., FIGS. 10B-12B), in such embodiments, can be constructed as anoptical scanner. The OMR identifier 410 o may be provided on theexterior surface of the bottom wall 210 b of the cassette's outerhousing 210 or any other suitable portion or area of the cassette 200that is capable of interfacing with the detector 370 of the autoinjector300.

The RF EMF device 410 rf and one or more OMR identifier labels 410 o canbe applied to the cassette before or after it is assembled with theprefilled drug container. This allows the RF EMF device 410 rf and/orone or more OMR identifier labels 410 o to include additionalinformation or programming, such as the date of manufacture, location ofmanufacture, expiration date of drug, drug temperature stabilizationtime in order to allow the drug to reach an optimal temperature prior toinjection), and autoinjector verification that the cassette 200 and drugare OEM components.

As shown in FIG. 13D, various other embodiments of the cassetteidentification arrangement 410 may comprise the one or more magnets 410m, the RF EMF emitter device 410 rf, the one or more OMR identifiers 410o and the tabs 410 t (and/or indentations 410 i) described earlier, eachdefining a portion of the code provided by the arrangement 410. In suchembodiments of the cassette identification arrangement, the detector 370of the autoinjector can be constructed with the appropriate switches,sensors, receivers, and/or scanners (e.g. FIGS. 10B-12B) to detect thecorresponding cassette elements of the cassette identificationarrangement 410.

The cassette identification arrangement 410 may also be used to controlaspects of the cassette manufacturing and packaging processes. FIG. 14shows a flow chart which shows an example of how a single production ormanufacturing line may be used to assemble different product lines usingthe cassette identification arrangement to control the assembly of theprefilled drug containers (containing a range of different drugs and/orfill levels) and then rout the assembled cassettes to the appropriatepackaging stations. Block 500 represents a single manufacturing linewhich may comprise a computer controlled manufacturing system and blocks502, 504, 506, and 508 may represent four unassembled cassettes in theline each having it own cassette identification arrangementconfiguration (1, 2, 3, or 4) of tabs, indentations, etc. Each of theunassembled cassettes 502, 504, 506, and 508 are to be assembled with adrug container having one of four different drugs (A, B, C, or D) thatmatches the cassette identification arrangement configuration (cassetteID configuration). In the embodiment shown in FIG. 14, the manufacturingsystem may be programmed such that cassette ID configuration 1identifies drug C, cassette ID configuration 2 identifies drug B,cassette ID configuration 3 identifies drug D, and cassette IDconfiguration identifies drug A.

In block 510, the manufacturing system of the line identifies thecassette ID configuration of each of the unassembled cassettes 502, 504,506, and 508. For each of the unassembled cassettes 502, 504, 506, and508, the system in block 512 selects a matching one of the drugcontainers 514, 516, 518, and 518 prefilled with drugs A, B, C, and D,respectively, using the identified cassette ID and assembles it with theunassembled cassette 502, 504, 506, and 508. Therefore, in block 512,unassembled cassette 502 with cassette ID configuration 1 may beassembled with drug container 518 prefilled with drug C to generateassembled cassette 522, unassembled cassette 504 with cassette IDconfiguration 2 may be assembled with drug container 516 prefilled withdrug B to generate assembled cassette 524, unassembled cassette 506 withcassette ID configuration 3 may be assembled with drug container 520prefilled with drug D to generate assembled cassette 526, andunassembled cassette 508 with cassette ID configuration 4 may beassembled with drug container 514 prefilled with drug A to generateassembled cassette 528.

In block 530, the manufacturing system sorts assembled cassettes 522,524, 526, and 528 using their cassette ID configurations 1, 2, 3, and 4,respectively, and places them in packages 532, 534, 536, and 538 fordrugs C, B, D, and A, respectively.

FIGS. 15A and 15B collectively show an embodiment of the cassette cap240 of the cassette 200. The cassette cap 240 may function as a needleshield remover by engaging and gripping the needle shield 266 of thedrug container 260 in a manner that allows the user to remove the needleshield 266 from the drug container 260, prior to operating theautoinjector. Further, the cassette cap 240 may lockingly engage thecassette outer housing 210 so that it cannot be easily withdrawn fromthe cassette 200 unless the cassette 200 is properly installed in theautoinjector. This prevents the needle shield 266 from beinginadvertently removed from the drug container 260 when, for example, thecassette 200 is handled by the user. In addition, the presence of theshield remover 240 provides an indication that the cassette 200 has notbeen previously used or tampered with.

As shown in FIG. 15A, various embodiments of the cassette cap 240 maycomprise a hollow body 241 formed by a generally cylindrical portion 241c and a generally rectangular, key portion (key) 241 k disposed lateralto and merging with the cylindrical portion 241 c. The cassette cap 240may further comprise a tapered portion 242 that extends proximally fromthe cylindrical portion 241 c of the body 241. An outwardly extendingflange 244 terminates the tapered portion 242 and closes the cassettecap 240 at a proximal end 240 pe thereof. The flange 244 may function asa finger gripping member that allows a user to grip and pull thecassette cap 240 out of the cassette 200 to remove the needle shield 266from the drug container 260 after the cassette has been properlyinstalled in the autoinjector. To facilitate gripping and pulling of thecassette cap 240, the flange 244 may have a generally oblong shape whichis easily gripped by users with dexterity problems. An “arrow” icon 243may be provided on the tapered portion 242 of the cassette cap 240 toindicate the proper direction and orientation for inserting the cassetteinto the cassette door of the autoinjector.

The cylindrical portion 241 c and the key 241 k are open at a distal end240 de of the cassette cap 240. The open distal end of the cylindricalportion 241 c may be formed by a plurality of flexible, outwardly flaredtongues 245 t that define an expandable collar structure 245, whichmerges with the open distal end of the key 241 k. The expandable collarstructure 245 prevents the cassette cap 240 from being reinserted intothe cassette as shown in FIG. 15C. The cylindrical portion 241 c mayinclude flexible members 241 cf that allow the cylindrical portion 241 cto accept a metal insert 246 (FIG. 15B) that help engage and grip needleshield.

Referring again to FIG. 15A, the key 241 k may include an end wall 241ke that closes the proximal end thereof. The end wall 241 ke may extendslightly beyond a bottom wall 241 kb of the key 241 k, thereby forming astop 241 ks.

As shown in FIG. 16A, the proximal end wall 210 pe of the cassette outerhousing 210 may include a slot 214 s that extends from the aperture 214toward the bottom wall 210 b of the housing 210. The slot 214 s may besized and shaped so that it mates with the key 241 k of the cassette cap240 with the leading edge 2101 e of the outer housing bottom wall 210 bengaging the stop 241 ks of the cassette cap key 241 k, when thecassette cap 240 is in the cassette 200, thereby forming a cassette capanti-rotation structure. As shown in FIG. 16B, the anti-rotationstructure formed by the slot 214 s and key 241 k prevents the cassettecap 240 from being rotated or twisted around its longitudinal axis Zwhen the cassette cap 240 is in the cassette 200 (prior to needle shieldremoval) and thus, prevents rotation of the needle shield. This isimportant because rotation of the needle shield can result in cutting orcoring of the needle shield by the sharp end of the injection needle.Accordingly, the anti-rotation structure protects the needle shield frombeing damaged by the injection needle when the cassette cap 240 is inthe cassette 200. The stop 241 ks of the cassette cap key 241 k canlimit cassette cap 240 from being pushed along the longitudinal axis Zdistal towards the syringe, which also prevents the injection needlefrom penetrating and thereby damaging the needle shield.

Referring again to FIGS. 15A-15C, the bottom wall 241 kb of the key 241k may define a cassette cap locking structure formed by a distallyextending cantilever spring member 247 and a downwardly extendingprojection or lock tab 248 provided at the free end of the spring member247. The lock tab 248 may comprise an undercut formed by an inclinedsurface 248 s that defines an acute angle θ with the bottom surface 247b of the spring member 247.

As shown in FIGS. 15B and 15C, a metal tubular insert 246 may beprovided on an interior surface 241 i of the cylindrical body portion241 c for gripping the outer surface of the needle shield 266 so that itcan be withdrawn with the cassette cap 240. In various otherembodiments, the metal tubular insert 246 may be replaced by grippingteeth (not shown) formed on the interior surface 241 i of thecylindrical body portion 241 c. The cassette cap 240 may extend throughthe aperture 214 formed in the proximal end wall 210 pe of the outerhousing 210 of the cassette 200, which locates the flange or grippingmember 244 of the cassette cap 240 outside of the cassette 200. Thelocking structure of the cassette cap 240, formed by the cantileverspring member 247 and lock tab 248, may be disposed within the marginalproximal portion of the outer cassette housing 210, such that it locksthe cassette cap 240 in place in the cassette 200, in a tamper-resistantmanner. Locking may be facilitated by the cantilever spring member 247,which forces or biases the tab 248 into a lock aperture 210 a (FIG. 15C)that may be defined in the bottom wall 210 b of the outer housing 210 ofthe cassette 200. The lock tab 248 engaged with the lock aperture 210 aof the cassette outer housing 210, substantially prevents withdrawal ofthe cassette cap 240 from the cassette 200, unless the cassette 200 isproperly installed within the autoinjector. Because the cassette cap 240is attached to the needle shield 266 and locked within the cassette 200,the needle shield 266 may not be inadvertently removed from the syringe260, prior to proper installation in the autoinjector. The presence ofthe cassette cap 240 also provides an indication that the cassette 200has not been previously used or tampered with.

As shown in FIG. 15C, once the cassette cap 240 has been removed, thetongues 245 t of the expandable partial collar structure 245 expand orspread outwardly to prevent the cassette cap 240 and the needle shield266 attached thereto (not visible) from being re-inserted into theaperture 214 in the proximal end wall 210 pe of the cassette outerhousing 210. The absence of the cassette cap 240, therefore, provides anindication to the user that the cassette 200 has already been used orhas been tampered with.

FIG. 15D shows the cassette 200 after the access door of theautoinjector (both not visible) has been closed. As shown, the cassette200 is mounted on the support surface 301 s of the autoinjector chassis301. The chassis 301 may include a pin switch P, which is coupled to themicroprocessor of the autoinjector in a manner that allows signals ordata to be communicated to the microprocessor. Closure of theautoinjector cassette door may cause the pin switch P to press on thelock tab 248 (if certain conditions regarding the cassette are met aswill be explained further on), thereby bending the cantilever springmember 247 up, and releasing it from the lock tab 248 from the lock tabreceiving aperture 210 a (FIG. 15C) in the bottom wall 210B of the outercassette housing 210, thereby unlocking the cassette cap 240 from thecassette 200. With the locking tab 248 unlocked, a user can now graspthe gripping member 244 of the cassette cap 240 and withdraw it from thecassette 200 and the autoinjector, thereby removing the needle shield266 and uncovering the injection needle 265. When the pin switch Pengages the lock tab 248, it may also signal the autoinjector'smicroprocessor so that the autoinjector knows that the cassette 200 hasbeen installed.

As shown in FIG. 17A, various embodiments of the key 241 k may furtherinclude first and second pairs of arms or tabs 270 and 272, respectivelyextending out from the exterior side wall surfaces 241 ksw of the key241 k. As shown in FIG. 17B, the first pair of arms 270 may be disposedat or near the proximal end 241 kpe of the key 241 and the second pairof arms may be disposed at or near the distal end of the key 241 kde.The arms on each side of the key 241 k may be arranged in an inlinemanner, as shown in FIG. 17B.

Referring collectively to FIGS. 18A and 18B, various embodiments of thecassette outer housing 210 may comprise a pair of ribs 274 provided onthe interior side wall surfaces 210 is thereof. As shown in FIG. 18B,the key receiving slot 214 s formed in the proximal end wall 210 pe ofthe outer housing 210 may include slot extensions 214 sx that allow thefirst and second pairs of tabs 270 and 272, respectively to pass throughthe proximal end wall 210 pe of the cassette outer housing 210 when thecassette cap 240 is removed from the cassette 200. The slot extensions214 sx may be disposed immediately below the ribs 274 so that the tabs270, 272 engage the ribs 272, as will be explained below in furtherdetail.

As shown collectively in FIGS. 19A and 19B, the ribs 274 may extendlongitudinally from the proximal end wall 210 pe of the cassette outerhousing 210 and have a length L which allows the ribs to engage bothpairs of tabs 270, 272 when the cassette cap 240 is disposed in thecassette outer housing 200. As shown in FIG. 19A, the upper surfaces ofthe key tabs 270, 272 may engage the lower surfaces of the outer housingribs 274 when the cassette key 241 k is disposed in the cassette outerhousing 210, thereby forming a cassette cap anti-bending structure. Inother embodiments, the key tabs 270, 272 and ribs 267 may also beconstructed so that the lower surfaces of the key tabs 270, 272 engagethe upper surfaces of the outer housing ribs 274.

As shown in FIG. 20, the anti-bending structure prevents the cassettecap 240 from being flexed or bent in the vertical axis (X-axis) andhorizontal axis (Y-Axis.). The flexing or bending in the vertical orhorizontal axis may bend or damage the injection needle of the drugcontainer, therefore, the anti-bending structure prevents such bendingof or damage to the injection needle.

Referring now to FIG. 21, the autoinjector system 100 may be constructedto force users to execute the steps of the injection process in a safeand reliable order, which simplifies the operation of the autoinjectorsystem 100. By controlling the sequence of actions performed by theuser, the injection process can be made more reliable. Accordingly, invarious embodiments, the autoinjector system 100 is constructed to forceor cause the user to perform the following steps in sequence: insertingthe cassette 200 into the autoinjector 300; preparing the autoinjectorsystem 100 for injection; placing the autoinjector 300 on skin andstarting the injection process; and disposing of the used cassette 200and storing the autoinjector 300 for future use. Performing these stepsin sequence ensures autoinjector system reliability and user safety.

As described above, various embodiments of the autoinjector 300 andcassette 200 can comprise mechanical, electromechanical, and otherstructures that provide feedback signals to the microprocessor (notshown) of the autoinjector 300. The microprocessor may be programmedwith instructions (e.g., algorithm), which when executed thereby, allowthese signals to be evaluated by the microprocessor in order to enablethe autoinjector 300 to move through discrete logic “states” where theautoinjector system 100 is in a known configuration.

Referring now to FIG. 21 in conjunction with the flow chart of FIG. 22,an embodiment of the decision logic for controlling the variousfunctions of the autoinjector system 100, will be described. Thedecision logic forces the user to perform, in sequence, the steps of:inserting the cassette 200 into the autoinjector 300; preparing theautoinjector system 100 for injection; placing the autoinjector 300 onskin and starting the injection process; and disposing of the usedcassette 200 and storing the autoinjector 300 for future use.

Insertion of the Cassette into the Autoinjector

In block 500 (Off, Door Close, Cassette Out), prior to use, theautoinjector system 100 may be in a state where the only button that isactive is the one to initiate cassette door opening (eject button) andall other buttons are deactivated. This may force the autoinjectorsystem 100 only to respond to a single user action of pressing the ejectbutton at arrow 502 and all other actions may be ignored or may not bepossible. Once the cassette door 308 of the autoinjector 300 opens inblock 504, the user may insert the cassette 200 into the door. Invarious embodiments, the autoinjector 300 and cassette 200 may comprisecertain structures that allow the insertion of the cassette 200 only inthe correct orientation, such as one or more pins 215 on the cassette200, which interacts with a corresponding slot or pin 216 in thecassette door 308 of the autoinjector 300, as shown in FIG. 22, to allowinsertion only in the correct orientation and prevent insertion inorientations about the insertion axis (z axis). The cassette 200 mayalso have a tapered shape or other structure, which matches with thecassette door 308 of the autoinjector 300 to prevent rotation about thex axis.

While waiting for the user to insert the cassette 200, the autoinjector300 may transition to a known state in block 506 (Wait for Door Close A)where all other actions from the user with the exception of closing thedoor may be ignored such as pressing of start and eject buttons, etc.

This may force the user to either close the cassette door 308 with acassette 200 at arrow 508 to proceed with the injection process, orclose the door at arrow 510 without a cassette 200 as the autoinjectorsystem 100 moves to the previous known state of block 500. If the userchooses not to perform the required action, the autoinjector system 100continues to remain in the same state in block 512 (Door Open).

If the user inserts a cassette 200 of either an unknown configurationand/or a used cassette 200 into the cassette door 308 and closes atarrow 508, the autoinjector system 100 detects this state using, forexample the cassette identification arrangement described earlier, anddoes not allow the process to continue to the next state in block 516.Accordingly, the user is forced to insert a valid cassette 200 (knownconfiguration and unused) in the correct orientation into theautoinjector 300 in order to proceed.

Preparing the Autoinjector System for Injection

Once the cassette door 308 of the autoinjector 300 has been closed witha valid cassette 200, the autoinjector system 100 may move to an activestate in block 514 (Device Wakeup). The next step by the user in thisconfiguration is to remove the cassette cap 240 at arrow 518. Asdescribed above, the autoinjector system 100, in various embodiments,may be capable of detecting the presence or absence of the cassette cap240, and may also capable of monitoring a transition in the state of acassette cap remover switch that may be provided in the autoinjector 300from presence to absence. This transition may be used by theautoinjector system 100 to detect the removal of the cassette cap 240 bythe user and moving the autoinjector system 100 to the state of block520 (Cap Off). This may force the user to either remove the cassette cap240 at arrow 518 to proceed with the injection process, or abort theprocess by pressing the eject button at arrow 522, which opens the doorat block 524 (Open Door A) to allow the cassette 200 to be removed andreturns the autoinjector system 100 to the last known state at block 506(Wait for Door Close A). If the user chooses not to perform the requiredactions, the autoinjector system 100 continues to remains in the samestate at block 515 (Cassette in Sleep).

To ensure that these actions are truly intended by the user and notaccidentally initiated, the cassette cap removal and abort process mayrequire a committed action. Cassette cap removal may have a minimum pulloff force and pull off direction such that a user or patient needs topurposefully hold and pull off the cassette cap in order to remove theneedle shield. In other words, there is minimum removal force anddirection for removal (pulling straight down) such that the cassette capcannot be accidentally removed by normal handling. For the abortprocess, this may be achieved by requiring the user to press and holdthe eject button for a set time period at arrow 522 before the ejectprocess is initiated.

Place on Skin and Start the Injection Process

With a valid cassette 200 inserted into the autoinjector 300, thecassette cap 240 removed, and the autoinjector system 100 in the stateof block 520 (Cap Off), the user may place the autoinjector 300 on theinjection site (skin) at arrow 526. As described above, variousembodiments of the autoinjector 300 may include a skin sensor to allowthe autoinjector system 100 to detect proximity to the injection site.Therefore, the autoinjector system 100 can allow the user to proceedwith the injection process only when the injection site is detected. Asdescribed above, the microprocessor may be programmed with instructions,which allow the injection site presence to be indicated only when itdetects a continuous positive signal from the skin sensor. This ensuresthat the user is committed to the process and has a stable contact withthe injection site in order to move to the state of block 534 (Ready toInject). As described above, various embodiments of the cassette cap 240may have a structure that does not allow it to be reinserted into thecassette 200 once removed, thereby preventing the user from reinsertingthe cassette cap 240 and moving back to the prior state of block 514(Device Wakeup).

This forces the user to either hold the autoinjector 300 with a stablecontact at the injection site in order to proceed with the injectionprocess at block 534 or abort the process by pressing the eject buttonat arrow 522, which opens the door at block 524 to allow cassetteremoval and returns the autoinjector system 100 to the last known stateafter door opening at block 506 (Wait for Door Close A). If no stablesignal is obtained at arrow 530, the autoinjector system 100 maycontinue to remain in the state of block 520 (Cap Off). If injectionsite contact is lost at any point in time, the autoinjector system 100may return to the state of block 520 (Cap Off).

Once the above conditions are met and the autoinjector system 100 is inthe state of block 526 (Ready to Inject), the user in this configurationactivates the injection at arrow 532. Once initiated, the autoinjectorsystem 100 may reconfirm the cassette identification arrangement, skinsensor and the like, to confirm its expected configuration and onceconfirmed, it may automatically execute in sequence, needle injectionand drug extrusion in block 536 (Injection Progress), (NeedleRetraction) in block 538, (Injection Complete) in block 540, (PlungerRetraction) in block 542 and (Automatic Door Open) in block 544, toallow for cassette removal and disposal at block 548 (Wait for DoorClose B). Immediately after injection initiation by the user, all otherbuttons and switches on the autoinjector 300 may be disabled to preventunintentional activation of the buttons by the user during the injectionprocess.

During the injection process, the autoinjector system 100 uses sensors345 to constantly monitor the position of the plunger rod tip 342 a (seeFIG. 2H). A closed loop algorithm can be implemented using amicroprocessor 350 to maintain a constant target extrusion speed. Insuch a system, an initial motor current is first set based oncharacterization data for a particular speed target. As the extrusioncontinues, the position of the plunger rod tip 342 a is sampled at adesired frequency using sensor 345. A time delta t can be calculatedfrom the inverse of this frequency. Dividing the change in positionbetween samples by this time period between samples provides aninstantaneous speed for each sample. If the instant speed is greaterthan the target speed, the extrusion motor current is instantaneouslyadjusted to be lower. Conversely, if the instant speed is less than thetarget speed, the extrusion motor current limit is instantaneouslyadjusted to be higher. As a result, the target speed is maintainedthroughout injection. This closed loop system can be used to adjust forprocess inefficiencies of the syringe, plunger, or other components ofthe fluid path, and can compensate for variations in the viscosities ofthe drug. Further, the system 100 monitors the status of the injectionsite contact in block 564. The process may be terminated if at any pointin time there is a loss in injection site contact for a predeterminedtime (e.g., the user intentionally removes the autoinjector 300 from theinjection site or adjusts the position in such a way that a reliabledelivery process cannot be ensured). In addition, autoinjector system100 may check for various mechanical errors during the injection processin block 560 (Needle Jam Error), block 562 (Plunger Jam Error), block566 (Needle Retraction Error), block 568 (Device Failure), and block 570(Cassette Error).

Disposal of the Used Cassette and Storing the Autoinjector for FutureUse

Once the injection process is complete and the autoinjector system 100is in the state of block 548 (Wait for Door Close B), the user isexpected to remove and disposed of the used cassette 200 and close thecassette door 308 of the autoinjector 300 at arrow 550. In order toforce the user to do this, the autoinjector system 100 logic may beconfigured so that the user cannot close the cassette door 308 of theautoinjector 300 with a cassette 200 in the state of block 548. If doorclosure is attempted at arrow 552, the autoinjector system 100 maydetect the cassette 200 and immediately reopen the door at block 554.This may force the user to close the cassette door 308 without acassette 200 in order for the autoinjector system 100 to move to thestate of block 550 (Off) and store the autoinjector 300 for future use.If the user chooses not to perform the required action, the autoinjectorsystem 100 may continue to remain in the same state in block 556 (DoorOpen Sleep B).

Turning to FIGS. 23-26, an embodiment of the autoinjector 300 having alatching assembly 620 is provided. The autoinjector 300 may include ahousing 600 defining a shell and an inner volume 601. The shell mayinclude all or some of the features of the shell 302. A cassette, suchas cassette 200, may be removably disposed within the inner volume 601in a manner previously described. The door 308 may have a first end 308a that releasably couples to the housing 600 via a latching portion 604disposed at the first end 308 a. Specifically, the latching portion 604may include a groove 605 defined by a first surface 605 a, a secondsurface 605 b, a third surface 605 c, and a fourth surface 605 d andfurther may include a leading surface 606. The leading surface 606 maybe angled at approximately 45° relative to the elongated length of thedoor 308 to form a chamfered edge. Other angles are possible.

The drive mechanism 340 may further include a tube cap 610 coupled tothe end 342 a of the plunger rod 342. The tube cap 610 may bedimensioned similarly to the plunger rod 342, and may include a slidingmating portion 611 that slidably inserts into a bore 342 b formed at theend 342 a of the plunger rod 342. The sliding mating portion 611 may begenerally cylindrical in shape and may define a raised surface 611 athat may engage a gripping portion 342 c of the plunger rod 342. Thetube cap 610 further includes a piston-shaped portion 612 having agenerally cylindrical cross-section that may slide within a cylinder613. The piston-shaped portion 612 forms a first engaging surface 612 aand a second engaging surface 612 b disposed on opposing sides.

The latching assembly 620 may include a slotted latch housing 622 and alatch member 630. The slotted latch housing 622 is coupled to the shellof the housing 600. The slotted latch housing 622 has a first end 622 a,a second end 622 b, and a slot 624 extending between the first andsecond ends 622 a, 622 b. Further, the slotted latch housing 622 mayhave a protrusion 626 extending from an arm 625 positioned near the slot624.

The latch member 630 is slidably coupled to the slotted latch housing622 via a tab 632 that slidably engages the slot 624. The latch member630 may further include a bore 634 having a stop 636 to accommodate aresilient member 650, a facing surface 638, and a protrusion 640positioned near the facing surface 638 and extending outwardlytherefrom. The protrusion 640 may have a stepped configuration whereby afirst portion 640 a has a greater width than a second portion 640 b.Such a configuration may be used to provide clearance for variouscomponents of the autoinjector 300.

When the slotted latch housing 622 is coupled to the latch member 630,the resilient member 650 is positioned within the bore 634. The stop 636of the latch member 630 and the protrusion 626 of the latching assembly620 may be inserted into the resilient member 650 to limit its movement.In this configuration, the resilient member 650 urges the latch member630 towards the second end 622 b of the slotted latch housing 622. Thefacing surface 638 of the latch member 630 contacts the first engagingsurface 612 a of the tube cap 612. Due to the tube cap 612 being coupledto the plunger rod 342, lateral movement of the latch member 630 isconstrained, and thus is only permitted to move upon movement of theplunger rod 342.

When it is desired to insert a new cassette 200 into the housing 600, auser may actuate the drug extrusion drive 340 using any number ofapproaches. As illustrated in FIG. 24, where the latching assembly 620is in a disengaged position, actuation of the drug extrusion drive 340first causes the plunger rod 342 to retract, thus causing the tube cap610 to move with the plunger rod 342 in a direction away from the door308. Due to the engagement between the facing surface 638 of the latchmember 630 and the first engaging surface 612 a of the tube cap 612, thelatch member 630 slides towards the first end 622 a of the slotted latchhousing 622, and thus moves away and is disengaged from the door 308.Accordingly, the door 308 may either be completely removed from thehousing 600, or alternatively may be permitted to rotate outwards arounda hinged connection point (not shown). Accordingly, a user may insert acassette 200 into the inner volume 601.

In some examples, upon the door 308 being removed (or opened), the drugextrusion drive 340 may automatically cause the plunger 342 rod toadvance to a latching position. As FIGS. 25 and 26 illustrate, in thisconfiguration, the plunger rod 342 (and thus the tube cap 612) advancestowards the inner volume 601. The resilient member 650 then urges thelatch member 630 towards the second end 622 b of the slotted latchhousing 622 until the facing surface 638 of the latch member 630contacts the first engaging surface 612 a of the tube cap 610.Accordingly, as shown in FIG. 25, after the cassette 200 is loaded andthe door 308 is to be closed, the leading surface 606 of the latchingportion 604 contacts the protrusion 640. Because the leading portion 604is angled, inward rotation of the door 308 causes the leading portion604 to slide across the protrusion 640. Accordingly, the latch member630 may overcome the urging force of the resilient member 650, thus thelatch member 630 is urged towards the first end 622 a of the slottedlatch housing 622. Upon completely closing the door 308, the protrusion640 is no longer in contact with the leading portion 604, and thus theresilient member 650 again urges the latch member 630 towards the secondend 622 b of the slotted latch housing 622 until the protrusion 640 ispositioned within the groove 605. As such, and as illustrated in FIG.26, the second portion 640 b of the protrusion 640 restricts the door308 from being opened by contacting the first surface 605 a and thesecond surface 605 b.

In some examples, and as depicted in FIG. 24, the door 308 may bepositioned against the housing 600 prior to actuating the drivemechanism 340. As such, the drive mechanism may then be actuated,thereby causing the plunger rod 342 and thus the tube cap 610 to advancetowards the inner volume 601. This advancement allows the resilientmember 650 to urge the latch member 630 towards the second end 622 ofthe slotted latch housing 622, thereby engaging the latching portion 604of the door 308 to secure the door 308 to the housing 600.

In some examples (not shown), the drive mechanism 340 may cause theplunger rod 342 to advance to a third, ultimate position towards theinner volume 601. In this position, the latch member 630 is permitted tofurther advance towards the second end 622 b of the slotted latchhousing 622, thereby causing the protrusion 640 to be inserted furtherinto (and thus fully engaging) the groove 605. Such a configuration mayprovide a more secure coupling to the door 308, thereby fully preventingthe door 308 from being removed from the housing 600.

Those skilled in the art will recognize that a wide variety ofmodifications, alterations, and combinations can be made with respect tothe above described embodiments without departing from the scope of theinvention, and that such modifications, alterations, and combinationsare to be viewed as being within the ambit of the inventive concept.

The patent claims at the end of this patent application are not intendedto be construed under 35 U.S.C. § 112(f) unless traditionalmeans-plus-function language is expressly recited, such as “means foe”or “step foe” language being explicitly recited in the claim(s). Thesystems and methods described herein are directed to an improvement tocomputer functionality, and improve the functioning of conventionalcomputers.

Drug Information

As mentioned above, the container of the drug delivery device may befilled with a drug. This drug may be any one or combination of the drugslisted below, with the caveat that the following list should neither beconsidered to be all inclusive nor limiting. As used herein, the termdrug can be used interchangeably with other similar types of phrases andcan be used to mean any type of medicament, therapeutic ornon-therapeutic injectable such as traditional and non-traditionalpharmaceuticals, nutraceuticals, nutritional supplements, prodrugs(e.g., a compound or molecule which is administered in an inactive orless active state but is cleaved/processed to form the active druginside the recipient), biologics, biologically active compounds,biologically active molecules, biologically active agents, etc.

For example, the syringe may be filled with colony stimulating factors,such as granulocyte colony-stimulating factor (G-CSF). Such G-CSF agentsinclude, but are not limited to, Neupogen® (filgrastim) and Neulasta®(pegfilgrastim). In various other embodiments, the syringe may be usedwith various pharmaceutical products, such as an erythropoiesisstimulating agent (ESA), which may be in a liquid or a lyophilized form.An ESA is any molecule that stimulates erythropoiesis, such as Epogen®(epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta),Mircera® (methyoxy polyethylene glycol-epoetin beta), Hematide®,MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta),Silapo® (epoetin zeta), Binocrit® (epoetin alfa), epoetin alfa Hexal,Abseamed® (epoetin alfa), Ratioepo® (epoetin theta), Eporatio® (epoetintheta), Biopoin® (epoetin theta), epoetin alfa, epoetin beta, epoetinzeta, epoetin theta, and epoetin delta, as well as the molecules orvariants or analogs thereof as disclosed in the following patents orpatent applications, each of which is herein incorporated by referencein its entirety: U.S. Pat. Nos. 4,703,008; 5,441,868; 5,547,933;5,618,698; 5,621,080; 5,756,349; 5,767,078; 5,773,569; 5,955,422;5,986,047; 6,583,272; 7,084,245; and 7,271,689; and PCT Publication Nos.WO 91/05867; WO 95/05465; WO 96/40772; WO 00/24893; WO 01/81405; and WO2007/136752.

An ESA can be an erythropoiesis stimulating protein. As used herein,“erythropoiesis stimulating protein” means any protein that directly orindirectly causes activation of the erythropoietin receptor, forexample, by binding to and causing dimerization of the receptor.Erythropoiesis stimulating proteins include erythropoietin and variants,analogs, or derivatives thereof that bind to and activate erythropoietinreceptor; antibodies that bind to erythropoietin receptor and activatethe receptor; or peptides that bind to and activate erythropoietinreceptor. Erythropoiesis stimulating proteins include, but are notlimited to, epoetin alfa, epoetin beta, epoetin delta, epoetin omega,epoetin iota, epoetin zeta, and analogs thereof, pegylatederythropoietin, carbamylated erythropoietin, mimetic peptides (includingEMP1/hematide), and mimetic antibodies. Exemplary erythropoiesisstimulating proteins include erythropoietin, darbepoetin, erythropoietinagonist variants, and peptides or antibodies that bind and activateerythropoietin receptor (and include compounds reported in U.S.Publication Nos. 2003/0215444 and 2006/0040858, the disclosures of eachof which is incorporated herein by reference in its entirety) as well aserythropoietin molecules or variants or analogs thereof as disclosed inthe following patents or patent applications, which are each hereinincorporated by reference in its entirety: U.S. Pat. Nos. 4,703,008;5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078;5,773,569; 5,955,422; 5,830,851; 5,856,298; 5,986,047; 6,030,086;6,310,078; 6,391,633; 6,583,272; 6,586,398; 6,900,292; 6,750,369;7,030,226; 7,084,245; and 7,217,689; U.S. Publication Nos. 2002/0155998;2003/0077753; 2003/0082749; 2003/0143202; 2004/0009902; 2004/0071694;2004/0091961; 2004/0143857; 2004/0157293; 2004/0175379; 2004/0175824;2004/0229318; 2004/0248815; 2004/0266690; 2005/0019914; 2005/0026834;2005/0096461; 2005/0107297; 2005/0107591; 2005/0124045; 2005/0124564;2005/0137329; 2005/0142642; 2005/0143292; 2005/0153879; 2005/0158822;2005/0158832; 2005/0170457; 2005/0181359; 2005/0181482; 2005/0192211;2005/0202538; 2005/0227289; 2005/0244409; 2006/0088906; and2006/0111279; and PCT Publication Nos. WO 91/05867; WO 95/05465; WO99/66054; WO 00/24893; WO 01/81405; WO 00/61637; WO 01/36489; WO02/014356; WO 02/19963; WO 02/20034; WO 02/49673; WO 02/085940; WO03/029291; WO 2003/055526; WO 2003/084477; WO 2003/094858; WO2004/002417; WO 2004/002424; WO 2004/009627; WO 2004/024761; WO2004/033651; WO 2004/035603; WO 2004/043382; WO 2004/101600; WO2004/101606; WO 2004/101611; WO 2004/106373; WO 2004/018667; WO2005/001025; WO 2005/001136; WO 2005/021579; WO 2005/025606; WO2005/032460; WO 2005/051327; WO 2005/063808; WO 2005/063809; WO2005/070451; WO 2005/081687; WO 2005/084711; WO 2005/103076; WO2005/100403; WO 2005/092369; WO 2006/50959; WO 2006/02646; and WO2006/29094.

Examples of other pharmaceutical products for use with the device mayinclude, but are not limited to, antibodies such as Vectibix®(panitumumab), Xgeva™ (denosumab) and Prolia™ (denosamab); otherbiological agents such as Enbrel® (etanercept, TNF-receptor/Fc fusionprotein, TNF blocker), Neulasta® (pegfilgrastim, pegylated filgastrim,pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® (filgrastim, G-CSF,hu-MetG-CSF), and Nplate® (romiplostim); small molecule drugs such asSensipar® (cinacalcet). The device may also be used with a therapeuticantibody, a polypeptide, a protein or other chemical, such as an iron,for example, ferumoxytol, iron dextrans, ferric glyconate, and ironsucrose. The pharmaceutical product may be in liquid form, orreconstituted from lyophilized form.

Among particular illustrative proteins are the specific proteins setforth below, including fusions, fragments, analogs, variants orderivatives thereof:

OPGL specific antibodies, peptibodies, and related proteins, and thelike (also referred to as RANKL specific antibodies, peptibodies and thelike), including fully humanized and human OPGL specific antibodies,particularly fully humanized monoclonal antibodies, including but notlimited to the antibodies described in PCT Publication No. WO 03/002713,which is incorporated herein in its entirety as to OPGL specificantibodies and antibody related proteins, particularly those having thesequences set forth therein, particularly, but not limited to, thosedenoted therein: 9H7; 18B2; 2D8; 2E11; 16E1; and 22B3, including theOPGL specific antibodies having either the light chain of SEQUENCEIDENTIFICATION NUMBER:2 as set forth therein in FIG. 2 and/or the heavychain of SEQUENCE IDENTIFICATION NUMBER:4, as set forth therein in FIG.4, each of which is individually and specifically incorporated byreference herein in its entirety fully as disclosed in the foregoingpublication;

Myostatin binding proteins, peptibodies, and related proteins, and thelike, including myostatin specific peptibodies, particularly thosedescribed in U.S. Publication No. 2004/0181033 and PCT Publication No.WO 2004/058988, which are incorporated by reference herein in theirentirety particularly in parts pertinent to myostatin specificpeptibodies, including but not limited to peptibodies of the mTN8-19family, including those of SEQUENCE IDENTIFICATION NUMBERS:305-351,including TN8-19-1 through TN8-19-40, TN8-19 con1 and TN8-19 con2;peptibodies of the mL2 family of SEQUENCE IDENTIFICATIONNUMBERS:357-383; the mL15 family of SEQUENCE IDENTIFICATIONNUMBERS:384-409; the mL17 family of SEQUENCE IDENTIFICATIONNUMBERS:410-438; the mL20 family of SEQUENCE IDENTIFICATIONNUMBERS:439-446; the mL21 family of SEQUENCE IDENTIFICATIONNUMBERS:447-452; the mL24 family of SEQUENCE IDENTIFICATIONNUMBERS:453-454; and those of SEQUENCE IDENTIFICATION NUMBERS:615-631,each of which is individually and specifically incorporated by referenceherein in their entirety fully as disclosed in the foregoingpublication;

IL-4 receptor specific antibodies, peptibodies, and related proteins,and the like, particularly those that inhibit activities mediated bybinding of IL-4 and/or IL-13 to the receptor, including those describedin PCT Publication No. WO 2005/047331 or PCT Application No.PCT/US2004/37242 and in U.S. Publication No. 2005/112694, which areincorporated herein by reference in their entirety particularly in partspertinent to IL-4 receptor specific antibodies, particularly suchantibodies as are described therein, particularly, and withoutlimitation, those designated therein: L1H1; L1H2; L1H3; L1H4; L1H5;L1H6; L1H7; L1H8; L1H9; L1H10; L1H11; L2H1; L2H2; L2H3; L2H4; L2H5;L2H6; L2H7; L2H8; L2H9; L2H10; L2H11; L2H12; L2H13; L2H14; L3H1; L4H1;L5H1; L6H1, each of which is individually and specifically incorporatedby reference herein in its entirety fully as disclosed in the foregoingpublication;

Interleukin 1-receptor 1 (“IL1-R1”) specific antibodies, peptibodies,and related proteins, and the like, including but not limited to thosedescribed in U.S. Publication No. 2004/097712, which is incorporatedherein by reference in its entirety in parts pertinent to IL1-R1specific binding proteins, monoclonal antibodies in particular,especially, without limitation, those designated therein: 15CA, 26F5,27F2, 24E12, and 10H7, each of which is individually and specificallyincorporated by reference herein in its entirety fully as disclosed inthe aforementioned publication;

Ang2 specific antibodies, peptibodies, and related proteins, and thelike, including but not limited to those described in PCT PublicationNo. WO 03/057134 and U.S. Publication No. 2003/0229023, each of which isincorporated herein by reference in its entirety particularly in partspertinent to Ang2 specific antibodies and peptibodies and the like,especially those of sequences described therein and including but notlimited to: L1(N); L1(N) WT; L1(N) 1K WT; 2xL1(N); 2xL1(N) WT; Con4 (N),Con4 (N) 1K WT, 2xCon4 (N) 1K; L1C; L1C 1K; 2xL1C; Con4C; Con4C 1K;2xCon4C 1K; Con4-L1 (N); Con4-L1C; TN-12-9 (N); C17 (N); TN8-8(N);TN8-14 (N); Con 1 (N), also including anti-Ang 2 antibodies andformulations such as those described in PCT Publication No. WO2003/030833 which is incorporated herein by reference in its entirety asto the same, particularly Ab526; Ab528; Ab531; Ab533; Ab535; Ab536;Ab537; Ab540; Ab543; Ab544; Ab545; Ab546; A551; Ab553; Ab555; Ab558;Ab559; Ab565; AbF1AbFD; AbFE; AbFJ; AbFK; AbG1D4; AbGC1E8; AbH1C12;AblA1; AblF; AblK, AbIP; and AbIP, in their various permutations asdescribed therein, each of which is individually and specificallyincorporated by reference herein in its entirety fully as disclosed inthe foregoing publication;

NGF specific antibodies, peptibodies, and related proteins, and the likeincluding, in particular, but not limited to those described in U.S.Publication No. 2005/0074821 and U.S. Pat. No. 6,919,426, which areincorporated herein by reference in their entirety particularly as toNGF-specific antibodies and related proteins in this regard, includingin particular, but not limited to, the NGF-specific antibodies thereindesignated 4D4, 4G6, 6H9, 7H2, 14D10 and 14D11, each of which isindividually and specifically incorporated by reference herein in itsentirety fully as disclosed in the foregoing publication;

CD22 specific antibodies, peptibodies, and related proteins, and thelike, such as those described in U.S. Pat. No. 5,789,554, which isincorporated herein by reference in its entirety as to CD22 specificantibodies and related proteins, particularly human CD22 specificantibodies, such as but not limited to humanized and fully humanantibodies, including but not limited to humanized and fully humanmonoclonal antibodies, particularly including but not limited to humanCD22 specific IgG antibodies, such as, for instance, a dimer of ahuman-mouse monoclonal hLL2 gamma-chain disulfide linked to ahuman-mouse monoclonal hLL2 kappa-chain, including, but limited to, forexample, the human CD22 specific fully humanized antibody inEpratuzumab, CAS registry number 501423-23-0;

IGF-1 receptor specific antibodies, peptibodies, and related proteins,and the like, such as those described in PCT Publication No. WO06/069202, which is incorporated herein by reference in its entirety asto IGF-1 receptor specific antibodies and related proteins, includingbut not limited to the IGF-1 specific antibodies therein designatedL1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9, L10H10, L11H11,L12H12, L13H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, L20H20,L21H21, L22H22, L23H23, L24H24, L25H25, L26H26, L27H27, L28H28, L29H29,L30H30, L31H31, L32H32, L33H33, L34H34, L35H35, L36H36, L37H37, L38H38,L39H39, L40H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47,L48H48, L49H49, L50H50, L51H51, L52H52, and IGF-1R-binding fragments andderivatives thereof, each of which is individually and specificallyincorporated by reference herein in its entirety fully as disclosed inthe foregoing publication;

Also among non-limiting examples of anti-IGF-1R antibodies for use inthe methods and compositions of the present disclosure are each and allof those described in:

-   (i) U.S. Publication No. 2006/0040358 (published Feb. 23, 2006),    2005/0008642 (published Jan. 13, 2005), 2004/0228859 (published Nov.    18, 2004), including but not limited to, for instance, antibody 1A    (DSMZ Deposit No. DSM ACC 2586), antibody 8 (DSMZ Deposit No. DSM    ACC 2589), antibody 23 (DSMZ Deposit No. DSM ACC 2588) and antibody    18 as described therein;-   (ii) PCT Publication No. WO 06/138729 (published Dec. 28, 2006) and    WO 05/016970 (published Feb. 24, 2005), and Lu et al. (2004), J.    Biol. Chem. 279:2856-2865, including but not limited to antibodies    2F8, A12, and IMC-A12 as described therein;-   (iii) PCT Publication No. WO 07/012614 (published Feb. 1, 2007), WO    07/000328 (published Jan. 4, 2007), WO 06/013472 (published Feb. 9,    2006), WO 05/058967 (published Jun. 30, 2005), and WO 03/059951    (published Jul. 24, 2003);-   (iv) U.S. Publication No. 2005/0084906 (published Apr. 21, 2005),    including but not limited to antibody 7C10, chimaeric antibody    C7C10, antibody h7C10, antibody 7H2M, chimaeric antibody *7C10,    antibody GM 607, humanized antibody 7C10 version 1, humanized    antibody 7C10 version 2, humanized antibody 7C10 version 3, and    antibody 7H2HM, as described therein;-   (v) U.S. Publication Nos. 2005/0249728 (published Nov. 10, 2005),    2005/0186203 (published Aug. 25, 2005), 2004/0265307 (published Dec.    30, 2004), and 2003/0235582 (published Dec. 25, 2003) and Maloney et    al. (2003), Cancer Res. 63:5073-5083, including but not limited to    antibody EM164, resurfaced EM164, humanized EM164, huEM164 v1.0,    huEM164 v1.1, huEM164 v1.2, and huEM164 v1.3 as described therein;-   (vi) U.S. Pat. No. 7,037,498 (issued May 2, 2006), U.S. Publication    Nos. 2005/0244408 (published Nov. 30, 2005) and 2004/0086503    (published May 6, 2004), and Cohen, et al. (2005), Clinical Cancer    Res. 11:2063-2073, e.g., antibody CP-751,871, including but not    limited to each of the antibodies produced by the hybridomas having    the ATCC accession numbers PTA-2792, PTA-2788, PTA-2790, PTA-2791,    PTA-2789, PTA-2793, and antibodies 2.12.1, 2.13.2, 2.14.3, 3.1.1,    4.9.2, and 4.17.3, as described therein;-   (vii) U.S. Publication Nos. 2005/0136063 (published Jun. 23, 2005)    and 2004/0018191 (published Jan. 29, 2004), including but not    limited to antibody 19D12 and an antibody comprising a heavy chain    encoded by a polynucleotide in plasmid 15H12/19D12 HCA (γ4),    deposited at the ATCC under number PTA-5214, and a light chain    encoded by a polynucleotide in plasmid 15H12/19D12 LCF (κ),    deposited at the ATCC under number PTA-5220, as described therein;    and-   (viii) U.S. Publication No. 2004/0202655 (published Oct. 14, 2004),    including but not limited to antibodies PINT-6A1, PINT-7A2,    PINT-7A4, PINT-7A5, PINT-7A6, PINT-8A1, PINT-9A2, PINT-11A1,    PINT-11A2, PINT-11A3, PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12,    PINT-12A1, PINT-12A2, PINT-12A3, PINT-12A4, and PINT-12A5, as    described therein; each and all of which are herein incorporated by    reference in their entireties, particularly as to the aforementioned    antibodies, peptibodies, and related proteins and the like that    target IGF-1 receptors;

B-7 related protein 1 specific antibodies, peptibodies, related proteinsand the like (“B7RP-1,” also is referred to in the literature as B7H2,ICOSL, B7h, and CD275), particularly B7RP-specific fully humanmonoclonal IgG2 antibodies, particularly fully human IgG2 monoclonalantibody that binds an epitope in the first immunoglobulin-like domainof B7RP-1, especially those that inhibit the interaction of B7RP-1 withits natural receptor, ICOS, on activated T cells in particular,especially, in all of the foregoing regards, those disclosed in U.S.Publication No. 2008/0166352 and PCT Publication No. WO 07/011941, whichare incorporated herein by reference in their entireties as to suchantibodies and related proteins, including but not limited to antibodiesdesignated therein as follow: 16H (having light chain variable and heavychain variable sequences SEQUENCE IDENTIFICATION NUMBER:1 and SEQUENCEIDENTIFICATION NUMBER:7 respectively therein); 5D (having light chainvariable and heavy chain variable sequences SEQUENCE IDENTIFICATIONNUMBER:2 and SEQUENCE IDENTIFICATION NUMBER:9 respectively therein); 2H(having light chain variable and heavy chain variable sequences SEQUENCEIDENTIFICATION NUMBER:3 and SEQUENCE IDENTIFICATION NUMBER:10respectively therein); 43H (having light chain variable and heavy chainvariable sequences SEQUENCE IDENTIFICATION NUMBER:6 and SEQUENCEIDENTIFICATION NUMBER:14 respectively therein); 41H (having light chainvariable and heavy chain variable sequences SEQUENCE IDENTIFICATIONNUMBER:5 and SEQUENCE IDENTIFICATION NUMBER:13 respectively therein);and 15H (having light chain variable and heavy chain variable sequencesSEQUENCE IDENTIFICATION NUMBER:4 and SEQUENCE IDENTIFICATION NUMBER:12respectively therein), each of which is individually and specificallyincorporated by reference herein in its entirety fully as disclosed inthe foregoing publication;

IL-15 specific antibodies, peptibodies, and related proteins, and thelike, such as, in particular, humanized monoclonal antibodies,particularly antibodies such as those disclosed in U.S. Publication Nos.2003/0138421; 2003/023586; and 2004/0071702; and U.S. Pat. No.7,153,507, each of which is incorporated herein by reference in itsentirety as to IL-15 specific antibodies and related proteins, includingpeptibodies, including particularly, for instance, but not limited to,HuMax IL-15 antibodies and related proteins, such as, for instance,146B7;

IFN gamma specific antibodies, peptibodies, and related proteins and thelike, especially human IFN gamma specific antibodies, particularly fullyhuman anti-IFN gamma antibodies, such as, for instance, those describedin U.S. Publication No. 2005/0004353, which is incorporated herein byreference in its entirety as to IFN gamma specific antibodies,particularly, for example, the antibodies therein designated 1118;1118*; 1119; 1121; and 1121*. The entire sequences of the heavy andlight chains of each of these antibodies, as well as the sequences oftheir heavy and light chain variable regions and complementaritydetermining regions, are each individually and specifically incorporatedby reference herein in its entirety fully as disclosed in the foregoingpublication and in Thakur et al. (1999), Mol. Immunol. 36:1107-1115. Inaddition, description of the properties of these antibodies provided inthe foregoing publication is also incorporated by reference herein inits entirety. Specific antibodies include those having the heavy chainof SEQUENCE IDENTIFICATION NUMBER:17 and the light chain of SEQUENCEIDENTIFICATION NUMBER:18; those having the heavy chain variable regionof SEQUENCE IDENTIFICATION NUMBER:6 and the light chain variable regionof SEQUENCE IDENTIFICATION NUMBER:8; those having the heavy chain ofSEQUENCE IDENTIFICATION NUMBER:19 and the light chain of SEQUENCEIDENTIFICATION NUMBER:20; those having the heavy chain variable regionof SEQUENCE IDENTIFICATION NUMBER:10 and the light chain variable regionof SEQUENCE IDENTIFICATION NUMBER:12; those having the heavy chain ofSEQUENCE IDENTIFICATION NUMBER:32 and the light chain of SEQUENCEIDENTIFICATION NUMBER:20; those having the heavy chain variable regionof SEQUENCE IDENTIFICATION NUMBER:30 and the light chain variable regionof SEQUENCE IDENTIFICATION NUMBER:12; those having the heavy chainsequence of SEQUENCE IDENTIFICATION NUMBER:21 and the light chainsequence of SEQUENCE IDENTIFICATION NUMBER:22; those having the heavychain variable region of SEQUENCE IDENTIFICATION NUMBER:14 and the lightchain variable region of SEQUENCE IDENTIFICATION NUMBER:16; those havingthe heavy chain of SEQUENCE IDENTIFICATION NUMBER:21 and the light chainof SEQUENCE IDENTIFICATION NUMBER:33; and those having the heavy chainvariable region of SEQUENCE IDENTIFICATION NUMBER:14 and the light chainvariable region of SEQUENCE IDENTIFICATION NUMBER:31, as disclosed inthe foregoing publication. A specific antibody contemplated is antibody1119 as disclosed in the foregoing U.S. publication and having acomplete heavy chain of SEQUENCE IDENTIFICATION NUMBER:17 as disclosedtherein and having a complete light chain of SEQUENCE IDENTIFICATIONNUMBER:18 as disclosed therein;

TALL-1 specific antibodies, peptibodies, and the related proteins, andthe like, and other TALL specific binding proteins, such as thosedescribed in U.S. Publication Nos. 2003/0195156 and 2006/0135431, eachof which is incorporated herein by reference in its entirety as toTALL-1 binding proteins, particularly the molecules of Tables 4 and 5B,each of which is individually and specifically incorporated by referenceherein in its entirety fully as disclosed in the foregoing publications;

Parathyroid hormone (“PTH”) specific antibodies, peptibodies, andrelated proteins, and the like, such as those described in U.S. Pat. No.6,756,480, which is incorporated herein by reference in its entirety,particularly in parts pertinent to proteins that bind PTH;

Thrombopoietin receptor (“TPO-R”) specific antibodies, peptibodies, andrelated proteins, and the like, such as those described in U.S. Pat. No.6,835,809, which is herein incorporated by reference in its entirety,particularly in parts pertinent to proteins that bind TPO-R;

Hepatocyte growth factor (“HGF”) specific antibodies, peptibodies, andrelated proteins, and the like, including those that target theHGF/SF:cMet axis (HGF/SF:c-Met), such as the fully human monoclonalantibodies that neutralize hepatocyte growth factor/scatter (HGF/SF)described in U.S. Publication No. 2005/0118643 and PCT Publication No.WO 2005/017107, huL2G7 described in U.S. Pat. No. 7,220,410 and OA-5d5described in U.S. Pat. Nos. 5,686,292 and 6,468,529 and in PCTPublication No. WO 96/38557, each of which is incorporated herein byreference in its entirety, particularly in parts pertinent to proteinsthat bind HGF;

TRAIL-R2 specific antibodies, peptibodies, related proteins and thelike, such as those described in U.S. Pat. No. 7,521,048, which isherein incorporated by reference in its entirety, particularly in partspertinent to proteins that bind TRAIL-R2;

Activin A specific antibodies, peptibodies, related proteins, and thelike, including but not limited to those described in U.S. PublicationNo. 2009/0234106, which is herein incorporated by reference in itsentirety, particularly in parts pertinent to proteins that bind ActivinA;

TGF-beta specific antibodies, peptibodies, related proteins, and thelike, including but not limited to those described in U.S. Pat. No.6,803,453 and U.S. Publication No. 2007/0110747, each of which is hereinincorporated by reference in its entirety, particularly in partspertinent to proteins that bind TGF-beta;

Amyloid-beta protein specific antibodies, peptibodies, related proteins,and the like, including but not limited to those described in PCTPublication No. WO 2006/081171, which is herein incorporated byreference in its entirety, particularly in parts pertinent to proteinsthat bind amyloid-beta proteins. One antibody contemplated is anantibody having a heavy chain variable region comprising SEQUENCEIDENTIFICATION NUMBER:8 and a light chain variable region havingSEQUENCE IDENTIFICATION NUMBER:6 as disclosed in the foregoingpublication;

c-Kit specific antibodies, peptibodies, related proteins, and the like,including but not limited to those described in U.S. Publication No.2007/0253951, which is incorporated herein by reference in its entirety,particularly in parts pertinent to proteins that bind c-Kit and/or otherstem cell factor receptors;

OX40L specific antibodies, peptibodies, related proteins, and the like,including but not limited to those described in U.S. Publication No.2006/0002929, which is incorporated herein by reference in its entirety,particularly in parts pertinent to proteins that bind OX40L and/or otherligands of the OX40 receptor; and

Other exemplary proteins, including Activase® (alteplase, tPA); Aranesp®(darbepoetin alfa); Epogen® (epoetin alfa, or erythropoietin); GLP-1,Avonex® (interferon beta-1a); Bexxar® (tositumomab, anti-CD22 monoclonalantibody); Betaseron® (interferon-beta); Campath® (alemtuzumab,anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade®(bortezomib); MLN0002 (anti-α4β7 mAb); MLN1202 (anti-CCR2 chemokinereceptor mAb); Enbrel® (etanercept, TNF-receptor/Fc fusion protein, TNFblocker); Eprex® (epoetin alfa); Erbitux® (cetuximab,anti-EGFR/HER1/c-ErbB-1); Genotropin® (somatropin, Human GrowthHormone); Herceptin® (trastuzumab, anti-HER2/neu (erbB2) receptor mAb);Humatrope® (somatropin, Human Growth Hormone); Humira® (adalimumab);insulin in solution; Infergen® (interferon alfacon-1); Natrecor®(nesiritide; recombinant human B-type natriuretic peptide (hBNP);Kineret® (anakinra); Leukine® (sargamostim, rhuGM-CSF); LymphoCide®(epratuzumab, anti-CD22 mAb); Benlysta™ (lymphostat B, belimumab,anti-BlyS mAb); Metalyse® (tenecteplase, t-PA analog); Mircera® (methoxypolyethylene glycol-epoetin beta); Mylotarg® (gemtuzumab ozogamicin);Raptiva® (efalizumab); Cimzia® (certolizumab pegol, CDP 870); Soliris™(eculizumab); pexelizumab (anti-C5 complement); Numax® (MEDI-524);Lucentis® (ranibizumab); Panorex® (17-1A, edrecolomab); Trabio®(lerdelimumab); TheraCim hR3 (nimotuzumab); Omnitarg (pertuzumab, 2C4);Osidem® (IDM-1); OvaRex® (B43.13); Nuvion® (visilizumab); cantuzumabmertansine (huC242-DM1); NeoRecormon® (epoetin beta); Neumega®(oprelvekin, human interleukin-11); Neulasta® (pegylated filgastrim,pegylated G-CSF, pegylated hu-Met-G-CSF); Neupogen® (filgrastim, G-CSF,hu-MetG-CSF); Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonalantibody); Procrit® (epoetin alfa); Remicade® (infliximab, anti-TNFαmonoclonal antibody); Reopro® (abciximab, anti-GP IIb/IIIa receptormonoclonal antibody); Actemra® (anti-IL6 Receptor mAb); Avastin®(bevacizumab), HuMax-CD4 (zanolimumab); Rituxan® (rituximab, anti-CD20mAb); Tarceva® (erlotinib); Roferon-A®-(interferon alfa-2a); Simulect®(basiliximab); Prexige® (lumiracoxib); Synagis® (palivizumab); 146B7-CHO(anti-IL15 antibody, see U.S. Pat. No. 7,153,507); Tysabri®(natalizumab, anti-α4integrin mAb); Valortim® (MDX-1303, anti-B.anthracis protective antigen mAb); ABthrax™; Vectibix® (panitumumab);Xolair® (omalizumab); ETI211 (anti-MRSA mAb); IL-1 trap (the Fc portionof human IgG1 and the extracellular domains of both IL-1 receptorcomponents (the Type I receptor and receptor accessory protein)); VEGFtrap (Ig domains of VEGFR1 fused to IgG1 Fc); Zenapax® (daclizumab);Zenapax® (daclizumab, anti-IL-2Ra mAb); Zevalin® (ibritumomab tiuxetan);Zetia® (ezetimibe); Orencia® (atacicept, TACI-Ig); anti-CD80 monoclonalantibody (galiximab); anti-CD23 mAb (lumiliximab); BR2-Fc (huBR3/huFcfusion protein, soluble BAFF antagonist); CNTO 148 (golimumab, anti-TNFαmAb); HGS-ETR1 (mapatumumab; human anti-TRAIL Receptor-1 mAb);HuMax-CD20 (ocrelizumab, anti-CD20 human mAb); HuMax-EGFR (zalutumumab);M200 (volociximab, anti-α5β1 integrin mAb); MDX-010 (ipilimumab,anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1); anti-BR3 mAb; anti-C. difficileToxin A and Toxin B C mAbs MDX-066 (CDA-1) and MDX-1388); anti-CD22dsFv-PE38 conjugates (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC);anti-CD3 mAb (NI-0401); adecatumumab; anti-CD30 mAb (MDX-060); MDX-1333(anti-IFNAR); anti-CD38 mAb (HuMax CD38); anti-CD40L mAb; anti-CriptomAb; anti-CTGF Idiopathic Pulmonary Fibrosis Phase I Fibrogen (FG-3019);anti-CTLA4 mAb; anti-eotaxin1 mAb (CAT-213); anti-FGF8 mAb;anti-ganglioside GD2 mAb; anti-ganglioside GM2 mAb; anti-GDF-8 human mAb(MYO-029); anti-GM-CSF Receptor mAb (CAM-3001); anti-HepC mAb (HuMaxHepC); anti-IFNα mAb (MEDI-545, MDX-1103); anti-IGF1R mAb; anti-IGF-1RmAb (HuMax-Inflam); anti-IL12 mAb (ABT-874); anti-IL12/1L23 mAb (CNTO1275); anti-IL13 mAb (CAT-354); anti-IL2Ra mAb (HuMax-TAC); anti-IL5Receptor mAb; anti-integrin receptors mAb (MDX-018, CNTO 95); anti-IP10Ulcerative Colitis mAb (MDX-1100); anti-LLY antibody; BMS-66513;anti-Mannose Receptor/hCGβ mAb (MDX-1307); anti-mesothelin dsFv-PE38conjugate (CAT-5001); anti-PD1mAb (MDX-1106 (ONO-4538)); anti-PDGFRαantibody (IMC-3G3); anti-TGFβ mAb (GC-1008); anti-TRAIL Receptor-2 humanmAb (HGS-ETR2); anti-TWEAK mAb; anti-VEGFR/Flt-1 mAb; anti-ZP3 mAb(HuMax-ZP3); NVS Antibody #1; and NVS Antibody #2.

Also included can be a sclerostin antibody, such as but not limited toromosozumab, blosozumab, or BPS 804 (Novartis). Further included can betherapeutics such as rilotumumab, bixalomer, trebananib, ganitumab,conatumumab, motesanib diphosphate, brodalumab, vidupiprant,panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX or XGEVA. Additionally,included in the device can be a monoclonal antibody (IgG) that bindshuman Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9). Such PCSK9specific antibodies include, but are not limited to, Repatha®(evolocumab) and Praluent® (alirocumab), as well as molecules, variants,analogs or derivatives thereof as disclosed in the following patents orpatent applications, each of which is herein incorporated by referencein its entirety for all purposes: U.S. Pat. Nos. 8,030,547, 8,563,698,8,829,165, 8,859,741, 8,871,913, 8,871,914, 8,883,983, 8,889,834,8,981,064, 9,056,915, 8,168,762, 9,045,547, 8,030,457, 8,030,457,8,829,165, 8,981,064, 8,030,457, U.S. Publication No. 2013/0064825, U.S.Patent Application Publication No. 2012/0093818, U.S. Patent ApplicationPublication No. 2013/0079502, U.S. Patent Application Publication No.2014/0357850, U.S. Patent Application Publication No. 2011/0027287, U.S.Patent Application Publication No. 2014/0357851, U.S. Patent ApplicationPublication No. 2014/0357854, U.S. Patent Application Publication No.2015/0031870, U.S. Patent Application Publication No. 2013/0085265, U.S.Patent Application Publication No. 2013/0079501, U.S. Patent ApplicationPublication No. 2012/0213797, U.S. Patent Application Publication No.2012/0251544, U.S. Patent Application Publication No. 2013/0072665, U.S.Patent Application Publication No. 2013/0058944, U.S. Patent ApplicationPublication No. 2013/0052201, U.S. Patent Application Publication No.2012/0027765, U.S. Patent Application Publication No. 2015/0087819, U.S.Patent Application Publication No. 2011/0117011, U.S. Patent ApplicationPublication No. 2015/0004174, U.S. Provisional Patent Application No.60/957,668, U.S. Provisional Patent Application No. 61/008,965, U.S.Provisional Patent Application No. 61/010,630, U.S. Provisional PatentApplication No. 61/086,133, U.S. Provisional Patent Application No.61/125,304, U.S. Provisional Patent Application No. 61/798,970, U.S.Provisional Patent Application No. 61/841,039, U.S. Provisional PatentApplication No. 62/002,623, U.S. Provisional Patent Application No.62/024,399, U.S. Provisional Patent Application No. 62/019,729, U.S.Provisional Patent Application No. 62/067,637, U.S. patent applicationSer. No. 14/777,371, International Patent Application No.PCT/US2013/048714, International Patent Application No.PCT/US2015/040211, International Patent Application No.PCT/US2015/056972, International Patent Application Publication No.WO/2008/057457, International Patent Application Publication No.WO/2008/057458, International Patent Application Publication No.WO/2008/057459, International Patent Application Publication No.WO/2008/063382, International Patent Application Publication No.WO/2008/133647, International Patent Application Publication No.WO/2009/100297, International Patent Application Publication No.WO/2009/100318, International Patent Application Publication No.WO/2011/037791, International Patent Application Publication No.WO/2011/053759, International Patent Application Publication No.WO/2011/053783, International Patent Application Publication No.WO/2008/125623, International Patent Application Publication No.WO/2011/072263, International Patent Application Publication No.WO/2009/055783, International Patent Application Publication No.WO/2012/0544438, International Patent Application Publication No.WO/2010/029513, International Patent Application Publication No.WO/2011/111007, International Patent Application Publication No.WO/2010/077854, International Patent Application Publication No.WO/2012/088313, International Patent Application Publication No.WO/2012/101251, International Patent Application Publication No.WO/2012/101252, International Patent Application Publication No.WO/2012/101253, International Patent Application Publication No.WO/2012/109530, and International Patent Application Publication No.WO/2001/031007, International Patent Application Publication No.WO/2009/026558, International Patent Application Publication No.WO/2009/131740, International Patent Application Publication No.WO/2013/166448, and International Patent Application Publication No.WO/2014/150983.

Also included can be talimogene laherparepvec or another oncolytic HSVfor the treatment of melanoma or other cancers. Examples of oncolyticHSV include, but are not limited to talimogene laherparepvec (U.S. Pat.Nos. 7,223,593 and 7,537,924); OncoVEXGALV/CD (U.S. Pat. No. 7,981,669);OrienX010 (Lei et al. (2013), World J. Gastroenterol., 19:5138-5143);G207, 1716; NV1020; NV12023; NV1034 and NV1042 (Vargehes et al. (2002),Cancer Gene Ther., 9(12):967-978).

Also included are TIMPs. TIMPs are endogenous tissue inhibitors ofmetalloproteinases (TIMPs) and are important in many natural processes.TIMP-3 is expressed by various cells or and is present in theextracellular matrix; it inhibits all the major cartilage-degradingmetalloproteases, and may play a role in role in many degradativediseases of connective tissue, including rheumatoid arthritis andosteoarthritis, as well as in cancer and cardiovascular conditions. Theamino acid sequence of TIMP-3, and the nucleic acid sequence of a DNAthat encodes TIMP-3, are disclosed in U.S. Pat. No. 6,562,596, issuedMay 13, 2003, the disclosure of which is incorporated by referenceherein. Description of TIMP mutations can be found in U.S. PublicationNo. 2014/0274874 and PCT Publication No. WO 2014/152012.

Also included are antagonistic antibodies for human calcitoningene-related peptide (CGRP) receptor and bispecific antibody moleculethat target the CGRP receptor and other headache targets. Furtherinformation concerning these molecules can be found in PCT ApplicationNo. WO 2010/075238.

Additionally, a bispecific T cell engager antibody (BiTe), e.g.Blinotumomab can be used in the device. Alternatively, included can bean APJ large molecule agonist e.g., apelin or analogues thereof in thedevice. Information relating to such molecules can be found in PCTPublication No. WO 2014/099984.

In certain embodiments, the drug comprises a therapeutically effectiveamount of an anti-thymic stromal lymphopoietin (TSLP) or TSLP receptorantibody. Examples of anti-TSLP antibodies that may be used in suchembodiments include, but are not limited to, those described in U.S.Pat. Nos. 7,982,016, and 8,232,372, and U.S. Publication No.2009/0186022. Examples of anti-TSLP receptor antibodies include, but arenot limited to, those described in U.S. Pat. No. 8,101,182. Inparticularly preferred embodiments, the drug comprises a therapeuticallyeffective amount of the anti-TSLP antibody designated as A5 within U.S.Pat. No. 7,982,016.

While the present disclosure has been described in connection withvarious embodiments, it will be understood that the present disclosureis capable of further modifications. The present disclosure is intendedto cover any variations, uses, or adaptations of the disclosed subjectmatter following, in general, the principles of the present disclosure,and including such departures from the present disclosure as, within theknown and customary practice within the art to which the presentdisclosure pertains.

It is noted that the construction and arrangement of the drug deliverydevice and its various components and assemblies as shown in the variousexemplary embodiments is illustrative only. Although only a fewembodiments of the subject matter at issue have been described in detailin the present disclosure, those skilled in the art who review thepresent disclosure will readily appreciate that many modifications arepossible (e.g., variations in sizes, dimensions, structures, shapes andproportions of the various elements, values of parameters, mountingarrangements, use of materials, colors, orientations, etc.) withoutmaterially departing from the novel teachings and advantages of thesubject matter disclosed herein. For example, elements shown asintegrally formed may be constructed of multiple parts or elements, andvice versa. Also, the position of elements may be reversed or otherwisevaried, and the nature or number of discrete elements or positions maybe altered or varied. Accordingly, all such modifications are intendedto be included within the scope of the present disclosure as defined inthe appended claims. Furthermore, the order or sequence of any processor method steps may be varied or re-sequenced according to alternativeembodiments. Other substitutions, modifications, changes and omissionsmay be made in the design, operating conditions and arrangement of thevarious exemplary embodiments without departing from the scope of thepresent disclosure.

1. A drug delivery device comprising: a housing defining a shell and aninner volume; a cassette adapted to be removably disposed within theinner volume of the housing, the cassette further adapted to contain adrug to be administered to a user; a door coupled to the housing to atleast partially enclose the inner volume of the housing, the door havinga first end defining a latching portion; a drive mechanism at leastpartially disposed within the housing, the drive mechanism adapted toexert a force to urge the drug out the cassette; and a latching assemblycoupled to the drive mechanism, the latching assembly having a first endand a second end; wherein upon actuating the drive mechanism, the drivemechanism causes the latching assembly to engage the latching portion ofthe door to secure the door to the housing.
 2. The drug delivery deviceof claim 1, wherein the latching assembly includes: a tube cap movablycoupled to the drive mechanism, the tube cap having a first engagingsurface and a second engaging surface; a slotted latch housing coupledto the shell of the housing, the slotted latch housing having a firstend, a second end, and a slot extending between the first end and thesecond end; and a latch member slidably coupled to the slotted latchhousing and being movable along a length of the slot, the latch memberhaving a facing surface and a protrusion extending outwardly from thefacing surface to engage the latching portion of the door; wherein thefirst engaging surface of the tube cap engages the facing surface of thelatch member such that movement of the tube cap causes the latch memberto move along the length of the slot.
 3. The drug delivery device ofclaim 2, wherein the latch assembly is movable between at least a firstposition whereby the protrusion is disengaged from the latching portionof the door, a second position whereby the protrusion partially engagesthe latching portion of the door, and a third position whereby theprotrusion fully engages the latching portion of the door to restrictthe door from opening.
 4. The drug delivery device of claim 2, whereinthe latching portion of the door includes an angled leading surface toengage the protrusion.
 5. The drug delivery device of claim 2, whereinthe latch assembly further includes a resilient member to urge the latchmember towards the second end of the slotted latch housing.
 6. The drugdelivery device of claim 2, wherein the drive mechanism further includesa plunger rod, wherein the tube cap is slidably coupled to the plungerrod.
 7. (canceled)
 8. The drug delivery device of claim 1, wherein thedoor is coupled to the housing via a hinged connection.
 9. The drugdelivery device of any of claim 1, wherein the latching portion of thedoor includes a groove to restrict movement of the door.
 10. A latchingassembly for a drug delivery device, the latching assembly beingactuated by a drive mechanism at least partially disposed in the drugdelivery device, the latching assembly comprising: a tube cap movablycoupled to the drive mechanism, the tube cap having a first engagingsurface and a second engaging surface; a slotted latch housing adaptedto be coupled to the drug delivery device, the slotted latch housinghaving a first end, a second end, and a slot extending between the firstend and the second end; and a latch member slidably coupled to theslotted latch housing and being movable along a length of the slot, thelatch member having a facing surface and a protrusion extendingoutwardly from the facing surface to engage a latching portion of a drugdelivery device door; wherein the first engaging surface of the tube capengages the facing surface of the latch member such that movement of thetube cap causes the latch member to move along the length of the slot.11. The latching assembly of claim 10, wherein the latch assembly ismovable between at least a first position whereby the protrusion isdisengaged from the latching portion of the drug delivery device door, asecond position whereby the protrusion partially engages the latchingportion of the drug delivery device door, and a third position wherebythe protrusion fully engages the latching portion of the drug deliverydevice door to restrict the drug delivery device door from opening. 12.The latching assembly of claim 10, wherein the protrusion engages anangled leading surface of the drug delivery device door.
 13. Thelatching assembly of claim 10, wherein the latch assembly furtherincludes a resilient member urge the latch member towards the second endof the slotted latch housing.
 14. The latching assembly of claim 10,wherein tube cap is slidably coupled to a plunger rod of the drivemechanism.
 15. The latching assembly of claim 10, wherein the latchassembly is adapted to move to the second position upon removing thedrug delivery device door.
 16. The latching assembly of claim 10,wherein the protrusion engages a groove formed by latching portion ofthe drug delivery device door includes a groove to restrict movement ofthe drug delivery device door.
 17. A method of securing a removable doorto a drug delivery device having a housing defining a shell and an innervolume and a cassette removably disposed within the inner volume of thehousing and being adapted to contain a drug to be administered to a use,the method comprising: coupling a door to the housing to at leastpartially enclose the inner volume, the door having a first end defininga latching portion; at least partially disposing a drive mechanismwithin the housing, the drive mechanism adapted to exert a force to urgethe drug out of the cassette; coupling a latching assembly having afirst end and a second end to the drive mechanism such that uponactuating the drive mechanism, the drive mechanism causes the latchingassembly to engage the latching portion of the door to secure the doorto the housing.
 18. The method of claim 17, wherein the latchingassembly includes: a tube cap movably coupled to the drive mechanism,the tube cap having a first engaging surface and a second engagingsurface; a slotted latch housing coupled to the shell of the housing,the slotted latch housing having a first end, a second end, and a slotextending between the first end and the second end; and a latch memberslidably coupled to the slotted latch housing and being movable along alength of the slot, the latch member having a facing surface and aprotrusion extending outwardly from the facing surface to engage thelatching portion of the door; wherein the first engaging surface of thetube cap engages the facing surface of the latch member such thatmovement of the tube cap causes the latch member to move along thelength of the slot.
 19. The method of claim 18, further comprisingmoving the latch assembly between at least a first position whereby theprotrusion is disengaged from the latching portion of the door, a secondposition whereby the protrusion partially engages the latching portionof the door, and a third position whereby the protrusion fully engagesthe latching portion of the door to restrict the door from opening. 20.The method of claim 18, further comprising engaging the protrusion ofthe latch member with a leading surface of the latching portion of thedoor.
 21. The drug delivery device of claim 1, further comprising a drugdisposed in the cassette, the drug comprising etanercept.